Dynamic Adaption of Actin Stress Fibers in Response to Stretch

Abstract

Actin stress fibers are mechanosensitive structural elements that respond to stretching to regulate cell morphology, stress fiber alignment, signal transduction and cell function. Adherent cells maintain a level of prestress largely dependent on myosin contractility, suggesting that stress fibers self-adjust to an equilibrium level of stress. Here a quantitative model is developed to describe a potential mechanism for fibers to re-establish stress equilibrum in response to changes in fiber length. The model involves dynamic changes in fiber reference length regulated by myosin-actin cross bridging, where the force-velocity relationship for individual sarcomeres is expressed as a hyperbolic Hill-type model. Under static conditions, the basal level of fiber tension and pre-extension are determined by the number of sarcomeres bundled together in the fiber and the stall force of the constituent myosin filaments. Following a step increase in fiber length, tension initially increases elastically, but then relaxes with a characteristic time constant dependent on the rate of myosin cross bridge dynamics. Returning the fiber to the original length results in a drop in tension below equilibrium, followed by a relatively rapid return to equilibrium.The model predicts that stress fibers respond to cyclic stretch in a manner dependent on frequency, ATP concentration, equilibrium sarcomere length, and sarcomere stiffness with relaxation times ranging from 0.02 to 0.8 sec based on model parameter values extracted from the literature. The modeling results are consistent with various experimental findings and provide molecular insight into how stress fibers determine and maintain mechanical equilibrium in response to changes in length.