Modeling actin filament reorganization in endothelial cells subjected to cyclic stretch |
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Authors: | G Civelekoglu Y Tardy J-J Meister |
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Institution: | (1) Biomedical Engineering Laboratory, Swiss Federal Institute of Technology, PSE-Ecublens, 1015 Lausanne, Switzerland |
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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. |
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