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  • 1.
    Albet-Torres, Nuria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gunnarsson, Anders
    Persson, Malin
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Balaz, Martina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Höök, Fredrik
    Månsson, Alf
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Molecular motors on lipid bilayers and silicon dioxide: different driving forces for adsorption2010In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 6, no 14, p. 3211-3219Article in journal (Refereed)
    Abstract [en]

    Understanding how different types of interactions govern adsorption of the myosin motor fragment heavy meromyosin (HMM) onto different substrates is important in functional studies of actomyosin and for the development of motor powered lab-on-a-chip applications. In this study, we have combined in vitro motility assays and quartz crystal microbalance with dissipation (QCM-D) monitoring to investigate the underlying adsorption mechanisms of HMM onto supported lipid bilayers in comparison with pure and silanized SiO2. The QCM-D results, combined with data showing actin transportation by HMM adsorbed onto positively charged supported lipid bilayers, suggest reversible HMM surface adsorption via the negatively charged coiled-coil tail region. In contrast, the QCM-D data for HMM adsorption onto negatively charged lipids support a model according to which HMM adsorbs onto negatively charged surfaces largely via the positively charged actin binding regions. Adsorption studies at low (30-65 mM) and high (185-245 mM) ionic strengths onto piranha cleaned SiO2 surfaces (contact angle < 20 degrees) support this general model. However, unlike the situation for charged lipids, rinsing in high ionic strength solution caused only partial HMM desorption from SiO2, without restoration of actin propulsion by the remaining HMM molecules. This suggests that mechanisms other than electrostatic interactions are involved in the tethering of HMM heads to SiO2 surfaces. An expanded model for HMM adsorption is formulated on the basis of the data and the potential of the results for nanotechnological applications of actomyosin is discussed.

  • 2.
    Albet-Torres, Nuria
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Long-Term Storage of Surface-Adsorbed Protein Machines2011In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 27, no 11, p. 7108-7112Article in journal (Refereed)
    Abstract [en]

    The effective and simple long-term storage of complex functional proteins is critical in achieving commercially viable biosensors. This issue is particularly challenging in recently proposed types of nanobiosensors, where molecular-motor-driven transportation substitutes microfluidics and forms the basis for novel detection schemes. Importantly, therefore, we here describe that delicate heavy meromyosin (HMM)-based nanodevices (HMM motor fragments adsorbed to silanized surfaces and actin bound to HMM) fully maintain their function when stored at -20 degrees C for more than a month. The mechanisms for the excellent preservation of acto-HMM motor function upon repeated freeze thaw cycles are discussed. The results are important to the future commercial implementation of motor-based nanodevices and are of more general value to the long-term storage of any protein-based bionanodevice.

  • 3. Aveyard,, J
    et al.
    Hajne, J.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    van Delft,, F.C.M.J.M.
    van Zijl, J.
    Snijder, J.
    van den Heuvel,, F.C.
    Nicolau,, D.V.
    Actin motility confinement on micro/nanostructured surfaces.2013In: Proc. SPI 8587, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI, 858722 (February 22, 2013) / [ed] Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, SPIE - International Society for Optical Engineering, 2013, p. 858722-858727Conference paper (Refereed)
  • 4.
    Balaz, Martina
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Detection of small differences in actomyosin function using actin labeled with different phalloidin conjugates2005In: Analytical biochemistry, Vol. 338 (2), p. 224-236Article in journal (Refereed)
  • 5.
    Balaz, Martina
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Simultaneous studies of different actins in the in vitro motility assay2005In: Biophysical journal, Vol. 88 (1), p. 503A-503AArticle in journal (Refereed)
  • 6.
    Balaz, Martina
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Sundberg, Mark
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Persson, Malin
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Kvassman, Jan-Olov
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    "Effects of surface adsorption on catalytic activity of heavy meromyosin studied using fluorescent ATP analogue"2007In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 24, p. 4917-4934Article in journal (Refereed)
  • 7.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Actomyosin Interactions and Different Structural States of Actin Filaments2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 104, no 2, p. 480A-481AArticle in journal (Other academic)
  • 8.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Altered Structural State of Actin Filaments Upon MYOSIN II Binding2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2 Supplement 1, p. 299A-300A, article id 1499-PosArticle in journal (Other academic)
  • 9.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Analysis of Flexural Rigidity of Actin Filaments Propelled by Surface Adsorbed Myosin Motors2013In: Cytoskeleton, ISSN 1949-3584, Vol. 70, no 11, p. 718-728Article in journal (Refereed)
    Abstract [en]

    Actin filaments are central components of the cytoskeleton and the contractile machinery of muscle. The filaments are known to exist in a range of conformational states presumably with different flexural rigidity and thereby different persistence lengths. Our results analyze the approaches proposed previously to measure the persistence length from the statistics of the winding paths of actin filaments that are propelled by surface-adsorbed myosin motor fragments in the in vitro motility assay. Our results suggest that the persistence length of heavy meromyosin propelled actin filaments can be estimated with high accuracy and reproducibility using this approach provided that: (1) the in vitro motility assay experiments are designed to prevent bias in filament sliding directions, (2) at least 200 independent filament paths are studied, (3) the ratio between the sliding distance between measurements and the camera pixel-size is between 4 and 12, (4) the sliding distances between measurements is less than 50% of the expected persistence length, and (5) an appropriate cut-off value is chosen to exclude abrupt large angular changes in sliding direction that are complications, e.g., due to the presence of rigor heads. If the above precautions are taken the described method should be a useful routine part of in vitro motility assays thus expanding the amount of information to be gained from these. (c) 2013 Wiley Periodicals, Inc.

  • 10.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Karolinska Institutet ; McGill Univ, Canada.
    Rahman, Mohammad A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Delhi Technol Univ, India.
    Takatsuki, Hideyo
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 111, no 7, p. 1465-1477Article in journal (Refereed)
    Abstract [en]

    Actin filaments have key roles in cell motility but are generally claimed to be passive interaction partners in actin-myosin -based motion generation. Here, we present evidence against this static view based on an altered myosin-induced actin filament gliding pattern in an in vitro motility assay at varied [MgATP]. The statistics that characterize the degree of meandering of the actin filament paths suggest that for [MgATP] >= 0.25 mM, the flexural rigidity of heavy meromyosin (HMM)-propelled actin filaments is similar (without phalloidin) or slightly lower (with phalloidin) than that of HMM-free filaments observed in solution without surface tethering. When [MgATP] was reduced to <= 0.1 mM, the actin filament paths in the in vitro motility assay became appreciably more winding in both the presence and absence of phalloidin. This effect of lowered [MgATP] was qualitatively different from that seen when HMM was mixed with ATP-insensitive, N-ethylmaleimide-treated HMM (NEM-HMM; 25-30%). In particular, the addition of NEM-HMM increased a non-Gaussian tail in the path curvature distribution as well as the number of events in which different parts of an actin filament followed different paths. These effects were the opposite of those observed with reduced [MgATP]. Theoretical modeling suggests a 30-40% lowered flexural rigidity of the actin filaments at [MgATP] <= 0.1 mM and local bending of the filament front upon each myosin head attachment. Overall, the results fit with appreciable structural changes in the actin filament during actomyosin-based motion generation, and modulation of the actin filament mechanical properties by the dominating chemomechanical actomyosin state.

  • 11. Bunk, R
    et al.
    Klinth, Jeanna
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Montelius, L
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    An ordered in vitro motility assay for the study of actomyosin interactions.2002Conference paper (Refereed)
  • 12. Bunk, R
    et al.
    Klinth, Jeanna
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, L
    Imprinted tracks for biochemically powered motor proteins2002Conference paper (Refereed)
  • 13. Bunk, R
    et al.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Frölander, Kerstin
    Montelius, L
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Actomyosin motility on nanostructured resist polymers and silanes2003Conference paper (Refereed)
  • 14. Bunk, R
    et al.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, L
    Imprinted tracks for biochemically powered motor proteins?2002Conference paper (Refereed)
  • 15. Bunk, R
    et al.
    Sundberg, Mark
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Carlberg, P
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, L
    A biomolecular nanoscale traffic system: Controlled motion of quantum dot labelled motor proteins2004Other (Other academic)
  • 16. Bunk, Richard
    et al.
    Carlberg, P
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, Pär
    Sundberg, Mark
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, Lars
    Guiding molecular motors with nano-imprinted structures2005In: Japanese journal of applied physics. Part 1, Regular papers, short notes & review papers, Vol. 44 (5A), p. 3337-3340Article in journal (Refereed)
  • 17. Bunk, Richard
    et al.
    Klinth, Jeanna
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, Lars
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, Pär
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Actomyosin motility on nanostructured surfaces2003In: Biochemical and Biophysical Research Communications, Vol. 301, p. 783-788Article in journal (Refereed)
  • 18. Bunk, Richard
    et al.
    Klinth, Jeanna
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, Pär
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, Lars
    Towards a 'nano-traffic' system powered by molecular motors2003In: Microelectronic Engineering, Vol. 67-8, p. 899-904Article in journal (Refereed)
  • 19. Bunk, Richard
    et al.
    Sundberg, Mark
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, Pär
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, Lars
    Guiding motor-propelled molecules with nanoscale precision through silanized bi-channel structures2005In: Nanotechnology, Vol. 16 (6), p. 710-717Article in journal (Refereed)
  • 20. Chase, P. Bryant
    et al.
    Hong, Seunghun
    Månsson, Alf
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Xiong, Peng
    Bionanotechnology and Nanomedicine2012In: Journal of Biomedicine and Biotechnology, ISSN 1110-7243, E-ISSN 1110-7251, Vol. 2012, p. Article ID 763967-Article in journal (Other academic)
  • 21.
    Danielsson, Tom
    et al.
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Schreyer, Hendrik
    Kalmar County Hospital, Sweden.
    Woksepp, Hanna
    Kalmar County Hospital, Sweden.
    Johansson, Therese
    Kalmar County Hospital, Sweden.
    Bergman, Patrick
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Carlsson, Jörg
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Kalmar County Hospital, Sweden.
    Two-peaked increase of serum myosin heavy chain-α after triathlon suggests heart muscle cell death2019In: BMJ Open Sport & Exercise Medicine, ISSN 2055-7647, Vol. 5, article id e000486Article in journal (Refereed)
    Abstract [en]

    Objective It has been suggested that the mechanism behind cardiac troponin elevation after strenuous exercise is passage through a cell membrane with changed permeability rather than myocardial cell death. We hypothesised that an increase of cardiac specific myosin heavy chain-alpha (MHC-α; 224 kDa compared with cardiac troponin T’s (cTnT) 37 kDa) could hardly be explained by passage through a cell membrane.

    Methods Blood samples were collected from 56 athletes (15 female, age 42.5±9.7, range 24–70 years) before, directly after and on days 1–8 after an Ironman. Biomarkers (C reactive protein (CRP), cTnT, creatinekinase (CK), MHC-α, myoglobin (MG), creatinine (C) and N-terminal prohormone of brain natriuretic peptide (NTproBNP) were measured.

    Results The course of MHC-α concentration (μg/L) was 1.33±0.53 (before), 2.57±0.78 (directly after), 1.51±0.53 (day 1), 2.74±0.55 (day 4) and 1.83±0.76 (day 6). Other biomarkers showed a one-peaked increase with maximal values either directly after the race or at day 1: cTnT 76 ±80 ng/L (12–440; reference<15), NT-proBNP 776±684 ng/L (92–4700; ref.<300), CK 68±55 μkat/L (5–280; ref.<1.9), MG 2088±2350 μg/L (130–17 000; ref.<72) and creatinine 100±20 μmol/L (74–161; ref.<100), CRP 49±23 mg/L(15–119; ref.<5).

    Conclusion MHC-α exhibited a two-peaked increase which could represent a first release from the cytosolic pool and later from cell necrosis. This is the first investigation of MHC-α plasma concentration afterexercise.

  • 22. Edman, K A P
    et al.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Caputo, C
    The biphasic force-velocity relationship in frog muscle fibres and its evaluation in terms of cross-bridge function1997In: Journal of physiology, Vol. 503 (1), p. 141-156Article in journal (Refereed)
  • 23.
    Khrennikov, Andrei
    et al.
    Linnaeus University, Faculty of Technology, Department of Mathematics.
    Kozyrev, Sergei
    Russian Acad Sci, Russia.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hierarchical model of the actomyosin molecular motor based on ultrametric diffusion with drift2015In: Infinite Dimensional Analysis Quantum Probability and Related Topics, ISSN 0219-0257, Vol. 18, no 2, article id 1550013Article in journal (Refereed)
    Abstract [en]

    We discuss the approach to investigate molecular machines using systems of integro-differential ultrametric (p-adic) reaction-diffusion equations with drift. This approach combines the features of continuous and discrete dynamic models. We apply this model to investigation of actomyosin molecular motor. The introduced system of equations is solved analytically using p-adic wavelet theory. We find explicit stationary solutions and behavior in the relaxation regime.

  • 24.
    Klinth, Jeanna
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Arner, A
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding in vitro at saturating [MgATP]2003In: Journal of Muscle Research and Cell Motility, Vol. 24, p. 15-32Article in journal (Refereed)
  • 25.
    Klinth, Jeanna
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Bunk, R
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Montelius, L
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Reconstruction of motor protein order and function outside the living cell2002Conference paper (Refereed)
  • 26. Korten, Slobodanka
    et al.
    Albet-Torres, Nuria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Paderi, Francesca
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Diez, Stefan
    Korten, Till
    te Kronnie, Geertruy
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sample solution constraints on motor-driven diagnostic nanodevices2013In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 13, no 5, p. 866-876Article in journal (Refereed)
    Abstract [en]

    The last decade has seen appreciable advancements in efforts towards increased portability of lab-on-a-chip devices by substituting microfluidics with molecular motor-based transportation. As of now, first proof-of-principle devices have analyzed protein mixtures of low complexity, such as target protein molecules in buffer solutions optimized for molecular motor performance. However, in a diagnostic workup, lab-on-a-chip devices need to be compatible with complex biological samples. While it has been shown that such samples do not interfere with crucial steps in molecular diagnostics (for example antibody-antigen recognition), their effect on molecular motors is unknown. This critical and long overlooked issue is addressed here. In particular, we studied the effects of blood, cell lysates and solutions containing genomic DNA extracts on actomyosin and kinesin-microtubule-based transport, the two biomolecular motor systems that are most promising for lab-on-a-chip applications. We found that motor function is well preserved at defined dilutions of most of the investigated biological samples and demonstrated a molecular motor-driven label-free blood type test. Our results support the feasibility of molecular-motor driven nanodevices for diagnostic point-of-care applications and also demonstrate important constraints imposed by sample composition and device design that apply both to kinesin-microtubule and actomyosin driven applications.

  • 27.
    Korten, Till
    et al.
    Max-Planck-Institute for Molecular Cell Biology and Genetics, Dresden,.
    Månsson, Alf
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Diez, Stefan
    Max-Planck-Institute for Molecular Cell Biology and Genetics, Dresden,.
    Towards the application of cytoskeletal motor proteins in molecular detection and diagnostic devices2010In: Current Opinion in Biotechnology, ISSN 0958-1669, E-ISSN 1879-0429, Vol. 21, no 4, p. 477-488Article in journal (Refereed)
    Abstract [en]

    Over the past ten years, great advancements have been made towards using biomolecular motors for nanotechnological applications. In particular, devices using cytoskeletal motor proteins for molecular transport are maturing. First efforts towards designing such devices used motor proteins attached to micro-structured substrates for the directed transport of microtubules and actin filaments. Soon thereafter, the specific capture, transport and detection of target analytes like viruses were demonstrated. Recently, spatial guiding of the gliding filaments was added to increase the sensitivity of detection and allow parallelization. Whereas molecular motor powered devices have not yet demonstrated performance beyond the level of existing detection techniques, the potential is great: Replacing microfluidics with transport powered by molecular motors allows integration of the energy source (ATP) into the assay solution. This opens up the opportunity to design highly integrated, miniaturized, autonomous detection devices. Such devices, in turn, may allow fast and cheap on-site diagnosis of diseases and detection of environmental pathogens and toxins.

  • 28.
    Kumar, Saroj
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Milani, Gloria
    University of Padova, Italy.
    Takatsuki, Hideyo
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Lana, Tobia
    University of Padova, Italy.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Frasson, Chiara
    University of Padova, Italy.
    te Kronnie, Geertruy
    University of Padova, Italy.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sensing protein antigen and microvesicle analytes using high-capacity biopolymer nano-carriers2016In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, no 3, p. 836-846Article in journal (Refereed)
    Abstract [en]

    Lab-on-a-chip systems with molecular motor driven transport of analytes attached to cytoskeletal filament shuttles (actin filaments, microtubules) circumvent challenges with nanoscale liquid transport. However, the filaments have limited cargo-carrying capacity and limitations either in transportation speed (microtubules) or control over motility direction (actin). To overcome these constraints we here report incorporation of covalently attached antibodies into self-propelled actin bundles (nanocarriers) formed by cross-linking antibody conjugated actin filaments viafascin, a natural actin-bundling protein. We demonstrate high maximum antigen binding activity and propulsion by surface adsorbed myosin motors. Analyte transport capacity is tested using both protein antigens and microvesicles, a novel class of diagnostic markers. Increased incubation concentration with protein antigen in the 0.1–100 nM range (1 min) reduces the fraction of motile bundles and their velocity but maximum transportation capacity of >1 antigen per nm of bundle length is feasible. At sub-nanomolar protein analyte concentration, motility is very well preserved opening for orders of magnitude improved limit of detection using motor driven concentration on nanoscale sensors. Microvesicle-complexing to monoclonal antibodies on the nanocarriers compromises motility but nanocarrier aggregation via microvesicles shows unique potential in label-free detection with the aggregates themselves as non-toxic reporter elements.

  • 29.
    Kumar, Saroj
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Delhi Technol Univ, India.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Covalent and non-covalent chemical engineering of actin for biotechnological applications2017In: Biotechnology Advances, ISSN 0734-9750, E-ISSN 1873-1899, Vol. 35, no 7, p. 867-888Article, review/survey (Refereed)
    Abstract [en]

    The cytoskeletal filaments are self-assembled protein polymers with 8-25 nm diameters and up to several tens of micrometres length. They have a range of pivotal roles in eukaryotic cells, including transportation of intracellular cargoes (primarily microtubules with dynein and kinesin motors) and cell motility (primarily actin and myosin) where muscle contraction is one example. For two decades, the cytoskeletal filaments and their associated motor systems have been explored for nanotechnological applications including miniaturized sensor systems andlab-on-a-chip devices. Several developments have also revolved around possible exploitation of the filaments alone without their motor partners. Efforts to use the cytoskeletal filaments for applications often require chemical or genetic engineering of the filaments such as specific conjugation with fluorophores, antibodies, oligonucleotides or various macromolecular complexes e.g. nanoparticles. Similar conjugation methods are also instrumental for a range of fundamental biophysical studies. Here we review methods for non-covalent and covalent chemical modifications of actin filaments with focus on critical advantages and challenges of different methods as well as critical steps in the conjugation procedures. We also review potential uses of the engineered actin filaments in nanotechnological applications and in some key fundamental studies of actin and myosin function. Finally, we consider possible future lines of investigation that may be addressed by applying chemical conjugation of actin in new ways.

  • 30.
    Kumar, Saroj
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Albet-Torres, Nuria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Magnetic capture from blood rescues molecular motor function in diagnostic nanodevices2013In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 11, article id 14Article in journal (Refereed)
    Abstract [en]

    Background: Introduction of effective point-of-care devices for use in medical diagnostics is part of strategies to combat accelerating health-care costs. Molecular motor driven nanodevices have unique potentials in this regard due to unprecedented level of miniaturization and independence of external pumps. However motor function has been found to be inhibited by body fluids. Results: We report here that a unique procedure, combining separation steps that rely on antibody-antigen interactions, magnetic forces applied to magnetic nanoparticles (MPs) and the specificity of the actomyosin bond, can circumvent the deleterious effects of body fluids (e.g. blood serum). The procedure encompasses the following steps: (i) capture of analyte molecules from serum by MP-antibody conjugates, (ii) pelleting of MP-antibody-analyte complexes, using a magnetic field, followed by exchange of serum for optimized biological buffer, (iii) mixing of MP-antibody-analyte complexes with actin filaments conjugated with same polyclonal antibodies as the magnetic nanoparticles. This causes complex formation: MP-antibody-analyte-antibody-actin, and magnetic separation is used to enrich the complexes. Finally (iv) the complexes are introduced into a nanodevice for specific binding via actin filaments to surface adsorbed molecular motors (heavy meromyosin). The number of actin filaments bound to the motors in the latter step was significantly increased above the control value if protein analyte (50-60 nM) was present in serum (in step i) suggesting appreciable formation and enrichment of the MP-antibody-analyte-antibody-actin complexes. Furthermore, addition of ATP demonstrated maintained heavy meromyosin driven propulsion of actin filaments showing that the serum induced inhibition was alleviated. Detailed analysis of the procedure i-iv, using fluorescence microscopy and spectroscopy identified main targets for future optimization. Conclusion: The results demonstrate a promising approach for capturing analytes from serum for subsequent motor driven separation/detection. Indeed, the observed increase in actin filament number, in itself, signals the presence of analyte at clinically relevant nM concentration without the need for further motor driven concentration. Our analysis suggests that exchange of polyclonal for monoclonal antibodies would be a critical improvement, opening for a first clinically useful molecular motor driven lab-on-a-chip device.

  • 31.
    Kumar, Saroj
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Lard, Mercy
    Lund University.
    Kronnie, Geertruy Te
    University of Padua, Italy.
    Linke, Heiner
    Lund University.
    Månsson, Alf
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Antibodies Covalently Immobilized on Actin Filaments for Fast Myosin Driven Analyte Transport2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10, article id e46298Article in journal (Refereed)
    Abstract [en]

    Biosensors would benefit from further miniaturization, increased detection rate and independence from external pumps and other bulky equipment. Whereas transportation systems built around molecular motors and cytoskeletal filaments hold significant promise in the latter regard, recent proof-of-principle devices based on the microtubule-kinesin motor system have not matched the speed of existing methods. An attractive solution to overcome this limitation would be the use of myosin driven propulsion of actin filaments which offers motility one order of magnitude faster than the kinesin-microtubule system. Here, we realized a necessary requirement for the use of the actomyosin system in biosensing devices, namely covalent attachment of antibodies to actin filaments using heterobifunctional cross-linkers. We also demonstrated consistent and rapid myosin II driven transport where velocity and the fraction of motile actin filaments was negligibly affected by the presence of antibody-antigen complexes at rather high density (>20 mu m(-1)). The results, however, also demonstrated that it was challenging to consistently achieve high density of functional antibodies along the actin filament, and optimization of the covalent coupling procedure to increase labeling density should be a major focus for future work. Despite the remaining challenges, the reported advances are important steps towards considerably faster nanoseparation than shown for previous molecular motor based devices, and enhanced miniaturization because of high bending flexibility of actin filaments.

  • 32.
    Lard, Mercy
    et al.
    Lund University.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Generosi, Johanna
    University of Copenhagen, Denmark.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, Heiner
    Lund University.
    Nanowire Interfacing with Molecular Motors: Light Guiding and Tunneling2013Conference paper (Other academic)
  • 33.
    Lard, Mercy
    et al.
    Lund Univ.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Generosi, Johanna
    Lund Univ / Univ Copenhagen.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, Heiner
    Molecular Motor Transport through Hollow Nanowires2014In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 14, no 6, p. 3041-3046Article in journal (Refereed)
    Abstract [en]

    Biomolecular motors offer self-propelled, directed transport in designed microscale networks and can potentially replace pump-driven nanofluidics. However, in existing systems, transportation is limited to the two-dimensional plane. Here we demonstrate fully one-dimensional (1D) myosin-driven motion of fluorescent probes (actin filaments) through 80 nm wide, Al2O3 hollow nanowires of micrometer length. The motor-driven transport is orders of magnitude faster than would be possible by passive diffusion. The system represents a necessary element for advanced devices based on gliding assays, for example, in lab-on-a-chip systems with channel crossings and in pumpless nanosyringes. It may also serve as a scaffold for bottom-up assembly of muscle proteins into actin ordered contractile units, mimicking the muscle sarcomere.

  • 34.
    Lard, Mercy
    et al.
    Lund University.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Generosi, Johanna
    Lund University.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, Heiner
    Lund University.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nanowire-Imposed Geometrical Control in Studies of Actomyosin Motor Function2015In: IEEE Transactions on Nanobioscience, ISSN 1536-1241, E-ISSN 1558-2639, Vol. 14, no 3, p. 289-297Article in journal (Refereed)
    Abstract [en]

    Recently, molecular motor gliding assays with actin and myosin from muscle have been realized on semiconductor nanowires coated with Al2O3. This opens for unique nanotechnological applications and novel fundamental studies of actomyosin motor function. Here, we provide a comparison of myosin-driven actin filament motility on Al2O3 to both nitrocellulose and trimethylchlorosilane derivatized surfaces. We also show that actomyosin motility on the less than 200 nm wide tips of arrays of Al2O3-coated nanowires can be used to control the number, and density, of myosin-actin attachment points. Results obtained using nanowire arrays with different inter-wire spacing are consistent with the idea that the actin filament sliding velocity is determined both by the total number and the average density of attached myosin heads along the actin filament. Further, the results are consistent with buckling of long myosin-free segments of the filaments as a factor underlying reduced velocity. On the other hand, the findings do not support a mechanistic role in decreasing velocity, of increased nearest neighbor distance between available myosin heads. Our results open up for more advanced studies that may use nanowire-based structures for fundamental investigations of molecular motors, including the possibility to create a nanowire-templated bottom-up assembly of 3D, muscle-like structures.

  • 35.
    Lard, Mercy
    et al.
    Lund University.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Delhi Technological University, India.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    te Kronnie, G.
    University of Padova, Italy.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, H.
    Lund University.
    Nano-structuring for molecular motor control2015In: Nano-Structures for Optics and Photonics: Optical Strategies for Enhancing Sensing, Imaging, Communication and Energy Conversion / [ed] Baldassare Di Bartolo, John Collins, Luciano Silvestri, Springer, 2015, p. 459-459Conference paper (Refereed)
    Abstract [en]

    The interaction of self-propelled biological molecular-motors and cytoskeletal filaments holds relevance for a variety of applications such as biosensing, drug screening, diagnostics and biocomputation. The use of these systems for lab-on-a-chip biotechnology applications shows potential for replacement of microfluidic flow by active, molecular-motor driven transport of filaments. The ability to control, confine and detect motile objects in such a system is possible by development of nanostructured surfaces for on-chip applications and fundamental studies of molecular-motors. Here we describe the localized detection (Lard et al., Sci Rep 3:1092, 2013) and fast transport of actin filaments by myosin molecular-motors (Lard et al., Biosens Biolectron 48(0):145–152, 2013), inserted within nanostructures, as a method for biocomputation and molecular concentration. These results include extensive myosin driven concentration of actin filaments on a miniaturized detector, of relevance for use of molecular-motors in a diagnostics platform. Also, we discuss the local enhancement of the fluorescence signal of filaments, relevant for use in a biocomputation device where tracking of potentially thousands of motile objects is of primary significance.

  • 36.
    Lard, Mercy
    et al.
    The Nanometer Structure Consortium (nmC@LU), Division of Solid State Physics, Lund University.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    te Kronnie, Geertruy
    Department of Women's and Children's Health, University of Padova.
    Linke, Heiner
    The Nanometer Structure Consortium (nmC@LU), Division of Solid State Physics, Lund University.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ultrafast molecular motor driven nanoseparation and biosensing2013In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 48, p. 145-152Article in journal (Refereed)
    Abstract [en]

    Portable biosensor systems would benefit from reduced dependency on external power supplies as well as from further miniaturization and increased detection rate. Systems built around self-propelled biological molecular motors and cytoskeletal filaments hold significant promise in these regards as they are built from nanoscale components that enable nanoseparation independent of fluidic pumping. Previously reported microtubule-kinesin based devices are slow, however, compared to several existing biosensor systems. Here we demonstrate that this speed limitation can be overcome by using the faster actomyosin motor system. Moreover, due to lower flexural rigidity of the actin filaments, smaller features can be achieved compared to microtubule-based systems, enabling further miniaturization. Using a device designed through optimization by Monte Carlo simulations, we demonstrate extensive myosin driven enrichment of actin filaments on a detector area of less than 10 μm2, with a concentration half-time of approximately 40 s. We also show accumulation of model analyte (streptavidin at nanomolar concentration in nanoliter effective volume) detecting increased fluorescence intensity within seconds after initiation of motor-driven transportation from capture regions. We discuss further optimizations of the system and incorporation into a complete biosensing workflow.

  • 37.
    Lard, Mercy
    et al.
    Lund University.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, Heiner
    Lund University.
    Tracking Actomyosin at Fluorescence Check Points2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, article id 1092Article in journal (Refereed)
    Abstract [en]

    Emerging concepts for on-chip biotechnologies aim to replace microfluidic flow by active, molecular-motor driven transport of cytoskeletal filaments, including applications in bio-simulation, biocomputation, diagnostics, and drug screening. Many of these applications require reliable detection, with minimal data acquisition, of filaments at many, local checkpoints in a device consisting of a potentially complex network of channels that guide filament motion. Here we develop such a detection system using actomyosin motility. Detection points consist of pairs of gold lines running perpendicular to nanochannels that guide motion of fluorescent actin filaments. Fluorescence interference contrast (FLIC) is used to locally enhance the signal at the gold lines. A cross-correlation method is used to suppress errors, allowing reliable detection of single or multiple filaments. Optimal device design parameters are discussed. The results open for automatic read-out of filament count and velocity in high-throughput motility assays, helping establish the viability of active, motor-driven on-chip applications.

  • 38. Leickt, Lisa
    et al.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Ohlson, Sten
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Prediction of affinity and kinetics in biomolecular interaction by affinity chromatography2001In: Analytical Biochemistry, Vol. 291, p. 102-108Article in journal (Refereed)
  • 39.
    Lindberg, Frida W.
    et al.
    Lund University.
    Korten, Till
    Tech Univ Dresden, Germany;Max Planck Inst Mol Cell Biol & Genet, Germany.
    Löfstrand, Anette
    Lund University.
    Rahman, Mohammad A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Graczyk, Mariusz
    Lund University.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linke, Heiner
    Lund University.
    Maximov, Ivan
    Lund University.
    Design and development of nanoimprint-enabled structures for molecular motor devices2019In: Materials Research Express, E-ISSN 2053-1591, Vol. 6, no 2, article id 025057Article in journal (Refereed)
    Abstract [en]

    Devices based on molecular motor-driven cytoskeletal filaments, e.g., actin filaments, have been developed both for biosensing and biocomputational applications. Commonly, these devices require nanoscaled tracks for guidance of the actin filaments which has limited the patterning technique to electron beam lithography. Thus, large scale systems become intractable to fabricate at a high throughput within a reasonable time-frame. We have studied the possibility to fabricate molecular motor-based devices using the high throughput, high resolution technique of nanoimprint lithography. Molecular motor-based devices require wide open regions (loading zones) to allow filaments to land for later propulsion into the nanoscale tracks. Such open zones are challenging to fabricate using nanoimprint lithography due to the large amount of material displaced in the process. We found that this challenge can be overcome by introducing nanoscaled pillars inside the loading zones, into which material can be displaced during imprint. By optimising the resist thickness, we were able to decrease the amount of material displaced without suffering from insufficient filling of the stamp. Furthermore, simulations suggest that the shape and positioning of the pillars can be used to tailor the overall cytoskeletal filament transportation direction and behaviour. This is a potentially promising design feature for future applications that however, requires further optimisations before experimental realisation.

  • 40.
    Lindberg, Frida W.
    et al.
    Lund University.
    Norrby, Marlene
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rahman, Mohammad A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Salhotra, Aseem
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Takatsuki, Hideyo
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jeppesen, Soren
    Lund University.
    Linke, Heiner
    Lund University.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Controlled Surface Silanization for Actin-Myosin and Biocompatibility of New Polymer Resists2018In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 34, no 30, p. 8777-8784Article in journal (Refereed)
    Abstract [en]

    Molecular motor-based nanodevices require organized cytoskeletal filament guiding along motility-promoting tracks, confined by motility-inhibiting walls. One way to enhance motility quality on the tracks, particularly in terms of filament velocity but also the fraction of motile filaments, is to optimize the surface hydrophobicity. We have investigated the potential to achieve this for the actin myosin II motor system on trimethylchlorosilane (TMCS)-derivatized SiO2 surfaces to be used as channel floors in nanodevices. We have also investigated the ability to supress motility on two new polymer resists, TU7 (for nanoimprint lithography) and CSAR 62 (for electron beam and deep UV lithography), to be used as channel walls. We developed a chemical-vapor deposition tool for silanizing SiO2 surfaces in a controlled environment to achieve different surface hydrophobicities (measured by water contact angle). In contrast to previous work, we were able to fabricate a wide range of contact angles by varying the silanization time and chamber pressure using only one type of silane. This resulted in a significant improvement of the silanization procedure, producing a predictable contact angle on the surface and thereby predictable quality of the heavy meromyosin (HMM)-driven actin motility with regard to velocity. We observed a high degree of correlation between the filament sliding velocity and contact angle in the range 10-86 degrees, expanding the previously studied range. We found that the sliding velocity on TU7 surfaces was superior to that on CSAR 62 surfaces despite similar contact angles. In addition, we were able to suppress the motility on both TU7 and CSAR 62 by plasma oxygen treatment before silanization. These results are discussed in relation to previously proposed surface adsorption mechanisms of HMM and their relationship to the water contact angle. Additionally, the results are considered for the development of actin-myosin based nanodevices with superior performance with respect to actin-myosin functionality.

  • 41.
    Matusovsky, Oleg S.
    et al.
    McGill Univ, Canada.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. McGill Univ, Canada.
    Cheng, Yu-Shu
    McGill Univ, Canada.
    Rassier, Dilson E.
    McGill Univ, Canada.
    High-speed AFM reveals subsecond dynamics of cardiac thin filaments upon Ca2+ activation and heavy meromyosin binding2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 33, p. 16384-16393Article in journal (Refereed)
    Abstract [en]

    High-speed atomic force microscopy (HS-AFM) can be used to study dynamic processes with real-time imaging of molecules within 1- to 5-nm spatial resolution. In the current study, we evaluated the 3-state model of activation of cardiac thin filaments (cTFs) isolated as a complex and deposited on a mica-supported lipid bilayer. We studied this complex for dynamic conformational changes 1) at low and high [Ca2+] (pCa 9.0 and 4.5), and 2) upon myosin binding to the cTF in the nucleotide-free state or in the presence of ATP. HS-AFM was used to directly visualize the tropo-myosin-troponin complex and Ca2+-induced tropomyosin movements accompanied by structural transitions of actin monomers within cTFs. Our data show that cTFs at relaxing or activating conditions are not ultimately in a blocked or activated state, respectively, but rather the combination of states with a prevalence that is dependent on the [Ca2+] and the presence of weakly or strongly bound myosin. The weakly and strongly bound myosin induce similar changes in the structure of cTFs as confirmed by the local dynamical displacement of individual tropomyosin strands in the center of a regulatory unit of cTF at the relaxed and activation conditions. The displacement of tropomyosin at the relaxed conditions had never been visualized directly and explains the ability of myosin binding to TF at the relaxed conditions. Based on the ratios of nonactivated and activated segments within cTFs, we proposed a mechanism of tropomyosin switching from different states that includes both weakly and strongly bound myosin.

  • 42. Montelius, L
    et al.
    Bunk, R
    Sundberg, Mark
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Rosengren-Holmberg, Jenny
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Carlberg, P
    Nicholls, Ian Alan
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Tågerud, Sven
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Omling, P
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Fabrication and characterization of fully biocompatible nanostructured surfaces allowing functional studies of molecular motors2004Other (Other academic)
  • 43.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Actomyosin based contraction: one mechanokinetic model from single molecules to muscle?2016In: Journal of Muscle Research and Cell Motility, ISSN 0142-4319, E-ISSN 1573-2657, Vol. 37, no 6, p. 181-194Article in journal (Refereed)
    Abstract [en]

    Bridging the gaps between experimental systems on different hierarchical scales is needed to overcome remaining challenges in the understanding of muscle contraction. Here, a mathematical model with well-characterized structural and biochemical actomyosin states is developed to that end. We hypothesize that this model accounts for generation of force and motion from single motor molecules to the large ensembles of muscle. In partial support of this idea, a wide range of contractile phenomena are reproduced without the need to invoke cooperative interactions or ad hoc states/transitions. However, remaining limitations exist, associated with ambiguities in available data for model definition e.g.: (1) the affinity of weakly bound cross-bridges, (2) the characteristics of the cross-bridge elasticity and (3) the exact mechanistic relationship between the force-generating transition and phosphate release in the actomyosin ATPase. Further, the simulated number of attached myosin heads in the in vitro motility assay differs several-fold from duty ratios, (fraction of strongly attached ATPase cycle times) derived in standard analysis. After addressing the mentioned issues the model should be useful in fundamental studies, for engineering of myosin motors as well as for studies of muscle disease and drug development.

  • 44.
    Månsson, Alf
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Actomyosin-ADP states, interhead cooperativity, and the force-velocity relation of skeletal muscle.2010In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 98, no 7, p. 1237-1246Article in journal (Refereed)
    Abstract [en]

    Despite intense efforts to elucidate the molecular mechanisms that determine the maximum shortening velocity and the shape of the force-velocity relationship in striated muscle, our understanding of these mechanisms remains incomplete. Here, this issue is addressed by means of a four-state cross-bridge model with significant explanatory power for both shortening and lengthening contractions. Exploration of the parameter space of the model suggests that an actomyosin-ADP state (AM( *)ADP) that is separated from the actual ADP release step by a strain-dependent isomerization is important for determining both the maximum shortening velocity and the shape of the force-velocity relationship. The model requires a velocity-dependent, cross-bridge attachment rate to account for certain experimental findings. Of interest, the velocity dependence for shortening contraction is similar to that for population of the AM( *)ADP state (with a velocity-independent attachment rate). This accords with the idea that attached myosin heads in the AM( *)ADP state position the partner heads for rapid attachment to the next site along actin, corresponding to the apparent increase in attachment rate in the model.

  • 45.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    ATP-Driven Mechanical Work Performed by Molecular Motors2013In: Encyclopedia of Biophysics / [ed] Gordon C. K. Roberts, Springer, 2013, p. 135-141Chapter in book (Other academic)
  • 46.
    Månsson, Alf
    Department of Pharmacology, University of Lund.
    Changes in force and stiffness during stretch of skeletal muscle fibers, effects of hypertonicity1989In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 56, no 2, p. 429-433Article in journal (Refereed)
    Abstract [en]

    Slow stretch ramps (velocity: 0.17 fiber lengths s-1) were imposed during fused tetanic contractions of intact muscle fibers of the frog (1.4–3.0 degrees C; sarcomere length: 2.12–2.21 microns). Instantaneous force-extension relations were derived both under isometric conditions and during slow stretch by applying fast (0.2 ms) length steps to the fiber. An increase in tonicity (98 mM sucrose added to control Ringer solution) led to significant reduction of the maximum isometric tension but at the same time to marked increase in the force enhancement during slow stretch. The maximum force level reached during the stretch was affected very little. Experiments on relaxed fibers showed that recruitment of passive parallel elastic components were of no relevance for these effects. Hypertonicity slightly increased the instantaneous stiffness of the active fiber both in the presence and in the absence of stretch. The total extension of the undamped fiber elasticity was considerably reduced by increased tonicity under isometric conditions but was only slightly affected during slow stretch. The change in length of the undamped cross-bride elasticity upon stretch was thus greater in the hypertonic than in the normotonic solution suggesting a greater increase in force per cross-bridge in the hypertonic medium. The contractile effects are consistent with the assumptions that hypertonicity reduces the capability of the individual cross-bridge to produce active force and, furthermore, that hypertonicity has only minor effects on the number of attached cross-bridges and the maximum load-bearing capacity of the individual bridge. 

  • 47.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Comparing models with one versus multiple myosin-binding sites per actin target zone: The power of simplicity2019In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 151, no 4, p. 578-592Article in journal (Refereed)
    Abstract [en]

    Mechanokinetic statistical models describe the mechanisms of muscle contraction on the basis of the average behavior of a large ensemble of actin-myosin motors. Such models often assume that myosin II motor domains bind to regularly spaced, discrete target zones along the actin-based thin filaments and develop force in a series of strain-dependent transitions under the turnover of ATP. The simplest models assume that there is just one myosin-binding site per target zone and a uniform spatial distribution of the myosin motor domains in relation to each site. However, most of the recently developed models assume three myosin-binding sites per target zone, and some models include a spatially explicit 3-D treatment of the myofilament lattice and thereby of the geometry of the actin-myosin contact points. Here, I show that the predictions for steady-state contractile behavior of muscle are very similar whether one or three myosin-binding sites per target zone is assumed, provided that the model responses are appropriately scaled to the number of sites. Comparison of the model predictions for isometrically contracting mammalian muscle cells suggests that each target zone contains three or more myosin-binding sites. Finally, I discuss the strengths and weaknesses of one-site spatially inexplicit models in relation to three-site models, including those that take into account the detailed 3-D geometry of the myofilament lattice. The results of this study suggest that single-site models, with reduced computational cost compared with multisite models, are useful for several purposes, e.g., facilitated molecular mechanistic insights.

  • 48.
    Månsson, Alf
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Cross-bridge movement and stiffness during the rise of tension in skeletal muscle - a theoretical analysis2000In: Journal of Muscle Research & Cell Motility, Vol. 21, p. 383-403Article in journal (Refereed)
  • 49.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    From Contractile Non-Uniformities and Mechanical Instabilities to Hypertrophic Cardiomyopathy2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2 Supplement 1, p. 444A-444A, article id 2234-PosArticle in journal (Other academic)
  • 50.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hypothesis and theory: mechanical instabilities and non-uniformities in hereditary sarcomere myopathies2014In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 5, article id 350Article in journal (Refereed)
    Abstract [en]

    Familial hypertrophic cardiomyopathy (HCM), due to point mutations in genes for sarcomere proteins such as myosin, occurs in 1/500 people and is the most common cause of sudden death in young individuals. Similar mutations in skeletal muscle, e.g., in the MYH7 gene for slow myosin found in both the cardiac ventricle and slow skeletal muscle, may also cause severe disease but the severity and the morphological changes are often different. In HCM, the modified protein function leads, over years to decades, to secondary remodeling with substantial morphological changes, such as hypertrophy, myofibrillar disarray, and extensive fibrosis associated with severe functional deterioration. Despite intense studies, it is unclear how the moderate mutation-induced changes in protein function cause the long-term effects. In hypertrophy of the heart due to pressure overload (e.g., hypertension), mechanical stress in the myocyte is believed to be major initiating stimulus for activation of relevant cell signaling cascades. Here it is considered how expression of mutated proteins, such as myosin or regulatory proteins, could have similar consequences through one or both of the following mechanisms: (1) contractile instabilities within each sarcomere (with more than one stable velocity for a given load), (2) different tension generating capacities of cells in series. These mechanisms would have the potential to cause increased tension and/or stretch of certain cells during parts of the cardiac cycle. Modeling studies are used to illustrate these ideas and experimental tests are proposed. The applicability of similar ideas to skeletal muscle is also postulated, and differences between heart and skeletal muscle are discussed.

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