The Role of Cellular Architecture in Vascular Smooth Muscle Function and Mechanics

Abstract

Recently, there has been a push towards clinical translation of biomechanical models of tissues by developing patient-specific models to predict disease outcomes. To accomplish this, it is necessary to understand the functional and mechanical properties of all the tissue components, including individual cells. In vasculature, tissues and cells have different structures based on their functional role. The principle goal of this work is to determine how cellular architecture influences function and mechanical properties. To test our hypotheses, we have developed in vitro models to study the relationship between structure and function at the tissue and cellular scale. We have developed microfluidic capture array device (MCAD) technology to study cell structure and function in 2D engineered vascular smooth muscle tissue and have developed cellular micro-biaxial stretching (CμBS) microscopy to determine single cell mechanical properties. First, using MCAD technology we were able to vary initial cell-cell contact during seeding to bias the cellular architecture in confluent vascular smooth muscle tissues. We found that tissues seeded using initially higher cell–cell contact conditions yielded tissues with more elongated cellular architecture which lead to greater contractile function in engineered tissues. We then used CμBS microscopy to determine the elastic anisotropic mechanical properties of individual cells, given by the strain energy density (SED) function. We found that smooth muscle cells (VSMCs) with native-like architectures are highly anisotropic and can be described by a SED based on the actin cytoskeletal organization. Then, we utilized CμBS microscopy to characterize loading and unloading mechanics of VSMCs. We found that VSMCs exhibit architecture-dependent anisotropic hysteresis where highly structured VSMCs exhibit typical hysteresis associated with viscous loss when stretched in the direction of actin fiber alignment but exhibit reverse hysteresis when stretched in the direction orthogonal to actin fiber alignment. We then modeled the observed hysteresis using two models: a quasi-linear (QLV) model and a Hill-type active fiber model and found that the QLV model was insufficient to characterize the anisotropic hysteresis but the Hill-type active fiber model was able to predict the anisotropic hysteresis in highly-organized VSMCs.