Effect of the Cell Orientation Angle on the Nucleus of a Cultured Vascular Smooth Muscle Cell Subjected to Uniaxial Stretching: A Finite Element Analysis

Abstract The media, a primary layer of the aortic wall, is rich in smooth muscle cells (SMCs) that regulate the vessel diameter and maintain the mechanical balance of the aortic ring in vivo. Embedded in the medial extracellular matrix, SMCs adapt to their surrounding mechanical environment via cyclic stretch during vascular contraction and relaxation. Thus, the circumferential stress that constantly acts on the hypertensive aorta is expected to further increase with increasing blood pressure (hypertension), resulting in a thickened medial wall. This thickening is considered an active biomechanical response of SMCs to maintain constant circumferential stress, ensuring homeostasis. Therefore, understanding how external forces or mechanical stimuli acting on SMCs are transmitted through intracellular components is crucial. Nuclei may sense mechanical changes through stress fibers (SFs) and focal adhesions (FAs). However, limited quantitative information exists regarding the mechanical contributions of SFs and FAs to whole-cell mechanical events, such as the response to uniaxial stretching. In this study, we developed a finite element model of a cultured vascular SMC with contractile SFs anchored on a silicone substrate via FAs and applied uniaxial stretching to investigate the mechanotransduction pathways in SMCs. We revealed that the initial orientation angle of the cell relative to the stretching direction strongly correlated with the resultant magnitude of the biomechanical forces acting on the nuclei surface exerted by the SFs.