title: Modeling actin filament reorganization in endothelial cells subjected to cyclic stretch.
abstract: Hemodynamic forces affect endothelial cell morphology and function. In particular, circumferential cyclic stretch of blood vessels, due to pressure changes during the cardiac cycle, is known to affect the endothelial cell shape, 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 filaments, reorganize in the direction which later becomes the cell's long axis. How this external mechanical stimulus is 'sensed' and transduced into the cell is still unknown. Here, we develop a mathematical model depicting the dynamics of actin filaments, and the influence of the cyclic stretch of the substratum based on the experimental evidence that external stimuli may be transduced inside the cell via transmembrane proteins which are coupled with actin filaments on the cytoplasmic side. Based on this view, we investigate two approaches describing the formulation of the transduction mechanisms involving the coupling between filaments and the membrane proteins. As a result, we find that the mechanical stimulus could cause the experimentally observed reorganization of the entire cytoskeleton simply by altering the dynamics of the filaments connected with the integral membrane proteins, as described in our model. Comparison of our results with previous studies of cytoskeletal dynamics reveals that the cytoskeleton, which, in the absence of the effect of stretch would maintain its isotropic distribution, slowly aligns with the precise direction set by the external stimulus. It is found that even a feeble stimulus, coupled with a strong internal dynamics, is sufficient to align actin filaments perpendicular to the direction of stretch.
authors.affiliation: Biomedical Engineering Laboratory, Swiss Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Civelekoglu
authors.forename: Y
authors.initials: Y
authors.lastname: Tardy
authors.forename: J J
authors.initials: JJ
authors.lastname: Meister
mesh_terms: D000199:Actins / Q000502:physiology*; D003198:Computer Simulation; D003599:Cytoskeleton / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D016014:Linear Models; D008955:Models, Cardiovascular; D013314:Stress, Mechanical
chemical_list: D000199:Actins