Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Thursday Speaker Abstracts

EMERGENT RHEOLOGY OF ACTOMYOSIN ENSEMBLES Madhusudhan Venkadesan 1 ; Dan Rivera 1 ; Khoi Nguyen 1 ; Boris Shraiman 2 ; 1 Yale University, Department of Mechanical Engineering and Materials Science, New Haven, CT, USA 2 University of California, Santa Barbara, Department of Physics, Kavli Institute for Theoretical Physics, Santa Barbara, CA, USA Muscle can transition between fluid-like and solid-like mechanical behavior depending upon its excitation and the external load. The isotonic force-velocity curve exemplifies the fluid-like behavior; load-dependence of the strain-rate is reminiscent of fluid rheology. However, for close to isometric force, muscle is solid-like and has negligible strain-rates for timescales 100–1000 times the intrinsic time constants associated with actomyosin dynamics. These rheological transitions are crucial for animal motor control capabilities and emerge from the molecular machinery that constitute muscle. We analyzed actomyosin ensemble models, ranging from two state myosin models to more complex five-state models, to pinpoint the source of these transitions and found that rheological transitions are an impossibility in current mechanochemical models of actomyosin ensembles. Furthermore, Edman [1] showed that muscle’s isotonic response shows nearly zero velocity for a range of loads around 0.8–1.3 times the isometric force, a property that leads to a solid-like rheology and behavior that is reminiscent of stiction (static friction). We found that this stiction-like state cannot be realized by current muscle models, whether they use Huxley’s simplified description of the actomyosin cycle or use spatially explicit computer simulations that include titin and myosin-binding protein C (MyBP C). Our findings show an open challenge in understanding the stiction-like behavior of muscle. Based on further analyses of spatially explicit models we propose a new hypothesis that elastic strain inhomogeneities within a sarcomere, partly influenced by titin and MyBP-C, may underlie emergent mechanochemical dynamics of actomyosin ensembles that lead to excitation-dependent rheological transitions. Acknowledgements NSF grants PHY-1748958, EFMA-1830870, and the Gordon and Betty Moore Foundation Grant 2919.02.References[1] K. A. Edman. The Journal of Physiology 404, 301 (1988).

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