Biophysical Society Thematic Meeting | Canterbury 2023

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

Poster Abstracts

21-POS Board 21 VALIDATION OF NOVEL INTERPRETATION OF FORCE RESPONSE OF CARDIAC MUSCLE TO QUICK STRETCH BY COMPUTER SIMULATIONS Bradley M Palmer 1 ; 1 University of Vermont, Molecular Physiology and Biophysics, Burlington, VT, USA The force response of demembranated mammalian cardiac muscle after a quick stretch is typically interpreted to represent the initial stretch of attached myosin crossbridges (phase 1), detachment of stretched crossbridges at an exponential rate (phase 2) followed by crossbridges reattaching in increased numbers due to length-dependent activation (phases 3 and 4). We propose that phase 2 additionally reflects an enhanced detachment rate of myosin crossbridges due to strain on the myosin crossbridge thereby explaining the nadir of the force response often observed below the original isometric force. To test this idea further, we used a computer model of crossbridge kinetics with attachment and detachment governed by Monte-Carlo methods. Unitary force was assigned when a crossbridge was attached, and an elastic force was generated when an attached crossbridge was displaced. The duration of detached crossbridge was governed by a first-order attachment rate f 0 , and the duration of attached crossbridge displaced a distance x was governed by the detachment rate g(x) = g 0 + g 1 x, where g 0 is the detachment rate with no displacement and g 1 indicates the sensitivity to displacement. An analytical solution suggested the exponential decay rate of phase 2 represents (f 0 + g 0 ) and the exponential rise rate of phase 3 represents g 0 . The depth of the nadir between phases 2 and 3 is proportional to g 1 and inversely proportional to g 0 . The computer simulations demonstrated that this interpretation is correct if the mechanical response is limited to a behavior displaying the homogeneous and additive properties of a linear system and if the myosin kinetics are reasonably represented by two states. This scheme for interpreting the force response to a quick stretch suggests that myosin detachment rate is enhanced with stretch and needs to be considered as contributing to the mechanical response of striated muscle subjected to length perturbations.

97