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Modeling mechanical force transmission via actin stress fibers

In medium and large arteries, endothelial cells (ECs) are subjected to a highly dynamic mechanical stress environment that regulates vascular physiology and pathology. It has been suggested that the actin stress fiber network allows rapid long distance transmission of forces within ECs; however, how this transmission occurs remains poorly understood. In the present work, we develop a mathematical model of force transmission via actin stress fibers and investigate the role of stress fiber organization in modulating the dynamics of this transmission. We describe stress fibers as uniformly prestressed viscoelastic filaments that directly link cell-surface mechanosensors such as integrins to internal structures such as the nucleus or cell-cell adhesion proteins. A system of reduced-order ordinary differential equations describing the motion of the stress fibers in response to an applied force is derived and solved. This system is used to study the dynamics of force transmission within a single EC as well as across cells in a monolayer. To characterize the dynamics of mechanical signal transmission, we compute the time evolution of the deformation of the stress fibers in response to either constant or time-dependent forcing. Consistent with experimental observations, our model predicts that actin stress fibers can mediate rapid force transmission and that stress fiber prestress is a critical determinant of the speed of force transmission. Our results also demonstrate that rapid force transmission is only possible when stress fibers are aligned and the applied force is largely orthogonal to the direction of fiber alignment. In contrast, rapid force transmission is not possible in cells whose stress fiber organization is isotropic. The large differences in force transmission between directionally aligned and isotropic stress fiber configurations suggest that stress fiber organization is a key determinant of EC mechano-sensitivity and mechano-responsiveness.

Author(s):

Cecile Gouget    
Ecole Polytechnique
France

Yongyun Hwang    
Imperial College London
United Kingdom

Abdul Barakat    
Ecole Polytechnique
France