Biophysical Society Thematic Meeting | Canterbury 2023

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

Monday Speaker Abstracts

MULTI-SCALE MODELING OF MUSCLE BIOPHYSICS: FROM MOLECULES TO POPULATIONS Andrew D. McCulloch 1,2,4 ; Abigail E Teitgen 1 ; Marcus Hock 1 ; Kimberly J McCabe 5 ; Swithin Razu 1 ; Annabelle N Fowler 1 ; Katherine Knaus 1 ; Stephanie Khuu 1 ; Matthew C Childers 4 ; Bahador Marzban 6 ; Gary Huber 3 ; J. Andrew McCammon 3 ; Daniel A Beard 6 ; Michael Regnier 4 ; 1 UC San Diego, Bioengineering, La Jolla, CA, USA 2 UC San Diego, Medicine, La Jolla, CA, USA 6 University of Michigan, Molecular and Integrative Physiology, Ann Arbor, MI, USA Multi-scale modeling of biological systems has advanced rapidly, driven in no small part by exceptional progress in mechanistic modeling of muscle biology and biophysics from molecular to population scales. Advances in deep learning promise to accelerate this progress, so that simulations and analyses previously considered infeasible may soon be routine. Here, we use the biophysics and biomechanics of cardiac and skeletal muscle as exemplars of a multi-scale modeling approach that spans: atomistic resolution models of molecular structure-function relations of myofilament proteins; sub-cellular models of myocyte biophysics; whole cell models of mechano-energetics, metabolism and cell signaling; multicellular agent-based models of cell cell and cell-matrix interactions regulating tissue state; continuum models of muscle and myocardial biomechanics and biophysics; organ-scale models of muscle-tendon and cardiac biomechanics; system level models of cardiovascular and limb segmental physiology and performance; and image-driven population-based models of heart disease and human movement phenotypes and their relationship to injury and disease progression and outcomes of therapeutic, training and preventative interventions. By considering the technical barriers to bridging these scales and the potential for emerging technologies to address these barriers, a vision for new multi-scale models of muscle and their applications to science and health is proposed. Supported by the Wu-Tsai Human Performance Alliance, NIBIB, NHLBI, and Additional Ventures 3 UC San Diego, Chemistry and Biochemistry, La Jolla, CA, USA 4 University of Washington, Bioengineering, Seattle, WA, USA 5 Simula Resesarch Laboratory, Oslo, Norway

49