Biophysical Society Thematic Meeting | Canterbury 2023

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

Thursday Speaker Abstracts

MULTISCALE MUSCLE MODELING: AN ORGANISMAL APPROACH Kiisa Nishikawa 1 ; Monica A Daley 2 ; Jill McNitt-Gray 3 ; Anne Silverman 4 ; Simon Sponberg 5 ; Madhusudhan Venkadesan 6 ; 1 Northern Arizona University, Biological Sciences, Flagstaff, AZ, USA 2 University of California at Irvine, Ecology & Evolutionary Biology, Irvine, CA, USA 3 University of Southern California, Health Sciences, Los Angeles, CA, USA 4 Colorado School of Mines, Mechanical Engineering, Golden, CO, USA Bottom-up approaches to muscle modeling have emphasized properties including calcium and cross-bridge kinetics based on parameters measured from in vitro and ex vivo experiments. These models perform fairly well at predicting forces produced by individual muscles during steady-state in vivo movements, but they perform much less well under dynamical and unsteady perturbed conditions. Recent in vivo measurements of unsteady, perturbed locomotion demonstrate 1) weak coupling of both timing and magnitude of muscle force from activation dynamics, and 2) the importance of strain dynamics (i.e., abrupt changes in strain rate) and interactions between strain dynamics and activation on the timing and magnitude of muscle force production. These effects are not explained by the current paradigm nor are they accurately predicted by current models, in part because experiments used to validate and refine those models have focused on isometric, isotonic and steady-state conditions. By performing ex vivo experiments that emulate changes in loading and strain rates that emulate in vivo unsteady locomotion, we demonstrate that isometric, isotonic and sinusoidal oscillations fail to predict in vivo muscle mechanics. We further show that strain transients and interactions between strain transients and activation have large effects on muscle force and work. These interactions suggest the view that muscle is a tunable active material where its force response to deformation depends on activation. The data help to reconcile CNS vs. preflex control of muscle force by suggesting that strain dynamics may provide tuning points at which muscles are most sensitive to activation. To advance understanding of muscle mechanics and improve the accuracy of multiscale models, we need to design multiscale experiments that describe interactions between dynamically varying strain and activation and extend existing models and theories to account for their interactions. 5 Georgia Institute of Technology, Physics, Atlanta, GA, USA 6 Yale University, Mechanical Engineering, New Haven, CT, USA

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