lnu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 26) Show all publications
Matusovsky, O. S., Månsson, A., Persson, M., Cheng, Y.-S. & Rassier, D. E. (2019). High-speed AFM reveals subsecond dynamics of cardiac thin filaments upon Ca2+ activation and heavy meromyosin binding. Proceedings of the National Academy of Sciences of the United States of America, 116(33), 16384-16393
Open this publication in new window or tab >>High-speed AFM reveals subsecond dynamics of cardiac thin filaments upon Ca2+ activation and heavy meromyosin binding
Show others...
2019 (English)In: 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) Published
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.

Place, publisher, year, edition, pages
National Academy of Sciences, 2019
Keywords
thin filaments, muscle contraction, HS-AFM
National Category
Biophysics Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-88826 (URN)10.1073/pnas.1903228116 (DOI)000481404300041 ()31358631 (PubMedID)
Available from: 2019-08-29 Created: 2019-08-29 Last updated: 2019-08-29Bibliographically approved
Månsson, A., Persson, M., Shalabi, N. & Rassier, D. E. (2019). Nonlinear Actomyosin Elasticity in Muscle?. Biophysical Journal, 116(2), 330-346
Open this publication in new window or tab >>Nonlinear Actomyosin Elasticity in Muscle?
2019 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 116, no 2, p. 330-346Article in journal (Refereed) Published
Abstract [en]

Cyclic interactions between myosin II motor domains and actin filaments that are powered by turnover of ATP underlie muscle contraction and have key roles in motility of nonmuscle cells. The elastic characteristics of actin-myosin cross-bridges are central in the force-generating process, and disturbances in these properties may lead to disease. Although the prevailing paradigm is that the cross-bridge elasticity is linear (Hookean), recent single-molecule studies suggest otherwise. Despite convincing evidence for substantial nonlinearity of the cross-bridge elasticity in the single-molecule work, this finding has had limited influence on muscle physiology and physiology of other ordered cellular actin-myosin ensembles. Here, we use a biophysical modeling approach to close the gap between single molecules and physiology. The model is used for analysis of available experimental results in the light of possible nonlinearity of the cross-bridge elasticity. We consider results obtained both under rigor conditions (in the absence of ATP) and during active muscle contraction. Our results suggest that a wide range of experimental findings from mechanical experiments on muscle cells are consistent with nonlinear actin-myosin elasticity similar to that previously found in single molecules. Indeed, the introduction of nonlinear cross-bridge elasticity into the model improves the reproduction of key experimental results and eliminates the need for force dependence of the ATP-induced detachment rate, consistent with observations in other single-molecule studies. The findings have significant implications for the understanding of key features of actin-myosin-based production of force and motion in living cells, particularly in muscle, and for the interpretation of experimental results that rely on stiffness measurements on cells or myofibrils.

Place, publisher, year, edition, pages
Cell Press, 2019
National Category
Biophysics
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-80278 (URN)10.1016/j.bpj.2018.12.004 (DOI)000456327100015 ()30606448 (PubMedID)2-s2.0-85059232890 (Scopus ID)
Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-08-29Bibliographically approved
Shalabi, N., Persson, M., Månsson, A., Vengallatore, S. & Rassier, D. E. (2017). Sarcomere Stiffness during Stretching and Shortening of Rigor Skeletal Myofibrils. Biophysical Journal, 113(12), 2768-2776
Open this publication in new window or tab >>Sarcomere Stiffness during Stretching and Shortening of Rigor Skeletal Myofibrils
Show others...
2017 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 113, no 12, p. 2768-2776Article in journal (Refereed) Published
Abstract [en]

In this study, we measured the stiffness of skeletal muscle myofibrils in rigor. Using a custom-built atomic force microscope, myofibrils were first placed in a rigor state then stretched and shortened at different displacements (0.1-0.3 mu m per sarcomere) and nominal speeds (0.4 and 0.8 mu m/s). During stretching, the myofibril stiffness was independent of both displacement and speed (average of 987 nN/mu m). During shortening, the myofibril stiffness was independent of displacement, but dependent on speed (1234 nN/mu m at 0.4 mu m/s; 1106 nN/mu m at 0.8 mu m/s). Furthermore, the myofibril stiffness during shortening was greater than that during stretching and the difference depended on speed (31 % at 0.4 mu m/s; 8% at 0.8 mu m/s). The results suggest that the myofibrils exhibit nonlinear viscoelastic properties that may be derived from myofibril filaments, similar to what has been observed in muscle fibers.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Biophysics
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-69765 (URN)10.1016/j.bpj.2017.10.007 (DOI)000418502800018 ()2-s2.0-85038393742 (Scopus ID)
Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2019-09-05Bibliographically approved
Bengtsson, E., Persson, M., Rahman, M. A., Kumar, S., Takatsuki, H. & Månsson, A. (2016). Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament. Biophysical Journal, 111(7), 1465-1477
Open this publication in new window or tab >>Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament
Show others...
2016 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 111, no 7, p. 1465-1477Article in journal (Refereed) Published
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.

National Category
Biophysics Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-58085 (URN)10.1016/j.bpj.2016.08.025 (DOI)000385471500013 ()27705769 (PubMedID)2-s2.0-85002888273 (Scopus ID)
Available from: 2016-11-11 Created: 2016-11-11 Last updated: 2019-08-12Bibliographically approved
Nicolau, D. V. ., Lard, M., Korten, T., van Delftf, F. C. M., Persson, M., Bengtsson, E., . . . Nicolau, D. V. (2016). Parallel computation with molecular-motor-propelled agents in nanofabricated networks. Proceedings of the National Academy of Sciences of the United States of America, 113(10), 2591-2596
Open this publication in new window or tab >>Parallel computation with molecular-motor-propelled agents in nanofabricated networks
Show others...
2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 10, p. 2591-2596Article in journal (Refereed) Published
Abstract [en]

The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology.

Keywords
parallel computing, molecular motors, NP complete, biocomputation, nanotechnology
National Category
Chemical Sciences
Research subject
Natural Science, Chemistry
Identifiers
urn:nbn:se:lnu:diva-51981 (URN)10.1073/pnas.1510825113 (DOI)000372013300025 ()26903637 (PubMedID)2-s2.0-84960532489 (Scopus ID)
External cooperation:
Available from: 2016-04-08 Created: 2016-04-08 Last updated: 2017-11-30Bibliographically approved
Nicolau, D. V. ., Lard, M., Korten, T., van Delft, F. C. M., Persson, M., Bengtsson, E., . . . Nicolau, D. V. (2016). REPLY TO EINARSSON: The computational power of parallel network exploration with many bioagents [Letter to the editor]. Proceedings of the National Academy of Sciences of the United States of America, 113(23), E3188-E3188
Open this publication in new window or tab >>REPLY TO EINARSSON: The computational power of parallel network exploration with many bioagents
Show others...
2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 23, p. E3188-E3188Article in journal, Letter (Refereed) Published
National Category
Chemical Sciences
Research subject
Natural Science, Chemistry
Identifiers
urn:nbn:se:lnu:diva-54681 (URN)10.1073/pnas.1605214113 (DOI)000377155400002 ()27226290 (PubMedID)
Available from: 2016-07-22 Created: 2016-07-21 Last updated: 2017-11-28Bibliographically approved
Kumar, S., Milani, G., Takatsuki, H., Lana, T., Persson, M., Frasson, C., . . . Månsson, A. (2016). Sensing protein antigen and microvesicle analytes using high-capacity biopolymer nano-carriers. The Analyst, 141(3), 836-846
Open this publication in new window or tab >>Sensing protein antigen and microvesicle analytes using high-capacity biopolymer nano-carriers
Show others...
2016 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, no 3, p. 836-846Article in journal (Refereed) Published
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.

National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-48641 (URN)10.1039/C5AN02377G (DOI)000368942600011 ()2-s2.0-84956748686 (Scopus ID)
Funder
Carl Tryggers foundation EU, FP7, Seventh Framework Programme
Available from: 2016-01-10 Created: 2016-01-10 Last updated: 2018-09-04Bibliographically approved
Bengtsson, E., Persson, M., Kumar, S. & Månsson, A. (2015). Altered Structural State of Actin Filaments Upon MYOSIN II Binding. Biophysical Journal, 108(2 Supplement 1), 299A-300A, Article ID 1499-Pos.
Open this publication in new window or tab >>Altered Structural State of Actin Filaments Upon MYOSIN II Binding
2015 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2 Supplement 1, p. 299A-300A, article id 1499-PosArticle in journal, Meeting abstract (Other academic) Published
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-47077 (URN)000362849100709 ()
Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2017-12-01Bibliographically approved
Lard, M., ten Siethoff, L., Kumar, S., Persson, M., te Kronnie, G., Månsson, A. & Linke, H. (2015). Nano-structuring for molecular motor control. In: Baldassare Di Bartolo, John Collins, Luciano Silvestri (Ed.), Nano-Structures for Optics and Photonics: Optical Strategies for Enhancing Sensing, Imaging, Communication and Energy Conversion. Paper presented at NATO Advanced Study Institute on Nano-Structures for Optics and Photonics: Optical Strategies for Enhancing, Sensing, Imaging, Communication, and Energy Conversion. Erice, Sicily, Italy, 4–19 July 2013 (pp. 459-459). Springer
Open this publication in new window or tab >>Nano-structuring for molecular motor control
Show others...
2015 (English)In: 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, Published 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.

Place, publisher, year, edition, pages
Springer, 2015
Series
NATO Science for Peace and Security Series B: Physics and Biophysics, ISSN 1874-6500
National Category
Nano Technology Biochemistry and Molecular Biology
Research subject
Natural Science, Chemistry
Identifiers
urn:nbn:se:lnu:diva-55335 (URN)10.1007/978-94-017-9133-5_28 (DOI)2-s2.0-84943311770 (Scopus ID)
Conference
NATO Advanced Study Institute on Nano-Structures for Optics and Photonics: Optical Strategies for Enhancing, Sensing, Imaging, Communication, and Energy Conversion. Erice, Sicily, Italy, 4–19 July 2013
Available from: 2016-08-11 Created: 2016-08-10 Last updated: 2017-04-21Bibliographically approved
Lard, M., ten Siethoff, L., Generosi, J., Persson, M., Linke, H. & Månsson, A. (2015). Nanowire-Imposed Geometrical Control in Studies of Actomyosin Motor Function. IEEE Transactions on Nanobioscience, 14(3), 289-297
Open this publication in new window or tab >>Nanowire-Imposed Geometrical Control in Studies of Actomyosin Motor Function
Show others...
2015 (English)In: IEEE Transactions on Nanobioscience, ISSN 1536-1241, E-ISSN 1558-2639, Vol. 14, no 3, p. 289-297Article in journal (Refereed) Published
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.

Keywords
Actin, aluminum oxide, in vitro motility assay, myosin, oxide-coated nanowire, sarcomere
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-46290 (URN)10.1109/TNB.2015.2412036 (DOI)000355321100005 ()25823040 (PubMedID)2-s2.0-84930670434 (Scopus ID)
Available from: 2015-09-14 Created: 2015-09-14 Last updated: 2017-12-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2819-3046

Search in DiVA

Show all publications