Anisotropic Mechanics of Vascular Smooth Muscle Cells Exposed to Dynamic Loads.

Vascular smooth muscle cells (VSMCs) are the most prevalent cells in the arterial wall. In vivo, arteries are exposed to dynamic biaxial loads; thus, when characterizing VSMC mechanics, it is important to determine their anisotropic and time-dependent mechanical properties. In this work, we use cellular microbiaxial stretching to apply complex deformations to single micropatterned VSMCs and measure the resulting changes in cell stress. Previously, cellular microbiaxial stretching has been used to measure VSMC mechanical properties in response to extensional strain. Here, we measure changes in cell stress in response to both extension and compression. Additionally, we measure immediate temporal changes in stress in response to cyclically applied deformations. We find that the VSMCs display clear hysteresis when incrementally stretched and compressed and demonstrate cycle-dependent stress-relaxation when exposed to cyclic step change extension and compression. Finally, we demonstrate that a Hill-type active fiber model is capable of replicating all observed hysteresis and cycle-dependent stress-relaxation, suggesting that the temporal stress-strain behavior of the cell is regulated by acto-myosin contraction and relaxation, rather than passive viscoelasticity. This study improves upon previous studies of cellular mechanical properties by considering cellular architecture and more complex deformations when measuring the time-dependent mechanical properties of VSMCs. These findings have important implications for modeling in mechanobiology as VSMCs are mechanosensitive and actively respond to changes in their mechanical environment to maintain vascular function.