血管内皮細胞の変形とストレスファイバーの配向に関する数値解析

抄録

This theoretical investigation of the mechanics of the vascular endothelial cells that line the luminal side of blood vessels focused on two points. First, we formulated a hypothesis on the orientation of stress fibers, i.e., bundles of actin filaments, under cyclic deformation, and used numerical simulation to predict their orientation under various types of substrate deformation. Second, we created a finite element model of cultured endothelial cells adhering to a substrate, i.e., a silicone membrane, and a vascular endothelial cell on the luminal side of a vascular wall, and used finite element analyses to determine the stress and strain under various types of deformation.
To predict the orientation of stress fibers, we hypothesized that they are oriented only in the direction in which the strain component in the fiber direction does not exceed the strain limit, either with maximum deformation of the substrate or during deformation of the substrate. We found that stress fibers have a minimum length during the process of substrate stretching, and investigated the importance of considering substrate deformation during cyclic stretching. The numerical simulation showed that the effect is small over the physiological range of cyclic deformation experienced in blood vessels. We also predicted the out-of-plane orientations of stress fibers during cycles of simple elongation, pure uniaxial stretching, and equibiaxial stretching. With cyclic equibiaxial stretching and the assumption of a certain cell height, the predicted orientation of stress fibers agreed with the reported range of orientation of the actin cytoskeleton.
Second, using finite element modeling and analyses, we modeled a cell adherent to a substrate and a vascular endothelial cell on the luminal side of the vascular wall. We assumed that a cell consists of a nucleus and cytoplasm, and that both are incompressible, isotropic, hyperelastic materials. We also assumed that the bottom surface of the cell completely attaches to the substrate surface. The analyses of the stress and strain in the cell showed that the strain was greatest at the substrate and decreased in higher positions in the cell; the amount of strain in the top region of the cell depended on its shape. Moreover, the existence of the nucleus caused a complicated distribution of stress and strain in the cytoplasm. This result provides important information for predicting the orientation of stress fibers with nonuniform deformation of a cell.