Modeling actin filament reorganization in endothelial cells subjected to cyclic stretch

Hemodynamic forces affect endothelial cell morphology and function. In part icular, circumferential cyclic stretch of blood vessels, due to pressure ch anges during the cardiac cycle, is known to affect the endothelial cell sha pe, mediating the alignment of the cells in the direction perpendicular to stretch. This change in cell shape proceeds a drastic reorganization at the internal level. The cellular scaffolding, mainly composed of actin filamen ts, reorganize in the direction which later becomes the cell's long axis. H ow this external mechanical stimulus is 'sensed' and transduced into the ce ll is still unknown. Here, we develop a mathematical model depicting the dy namics of actin filaments, and the influence of the cyclic stretch of the s ubstratum based on the experimental evidence that external stimuli may be t ransduced inside the cell via transmembrane proteins which are coupled with actin filaments on the cytoplasmic side. Based on this view, we investigat e two approaches describing the formulation of the transduction mechanisms involving the coupling between filaments and the membrane proteins. As a re sult, we find that the mechanical stimulus could cause the experimentally o bserved reorganization of the entire cytoskeleton simply by altering the dy namics of the filaments connected with the integral membrane proteins, as d escribed in our model. Comparison of our results with previous studies of c ytoskeletal dynamics reveals that the cytoskeleton, which, in the absence o f the effect of stretch would maintain its isotropic distribution, slowly a ligns with the precise direction set by the external stimulus. It is found that even a feeble stimulus, coupled with a strong internal dynamics, is su fficient to align actin filaments perpendicular to the direction of stretch . (C) 1998 Society for Mathematical Biology.