Empirically Determined Growth Laws for Vascular Smooth Muscle Cell Mechano-Adaptation

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There is often a disconnect between the available experimental measurements and those needed to populate functional mathematical models. This project will create a tightly integrated set of experiments and models to predict how arteries change in response to the internal loading of blood flow. The results of this work will be the framework needed to predict how the arterial system develops during growth. The results will be incorporated into the PI's graduate-level Tissue Mechanics course. In addition, the PI's undergraduate-level Biomechanics course will be integrated with an existing outreach program to 2nd graders at Harambee Elementary School where the young students learn some basic fundamentals of the engineering approaches to problem solving.Traditionally, mechano-adaptation models have employed phenomenological growth laws that connect arterial tissue or vascular smooth muscle cell (VSMC) stress with vessel remodeling. This approach can give important qualitative insight, but for the theory to be predictive, it needs to be better connected to vessel physiology. An examination of VSMC cell biology suggests that the simple growth laws commonly used are unlikely to universally describe VSMC mechano-adaptation. For example, VSMCs readily switch between two phenotypes (contractile and synthetic) with markedly different behaviors. This switching is particularly pronounced during remodeling, both adaptive and maladaptive, suggesting that it is a key step in the mechano-adaptation process. Additionally, vascular dysfunctions, such as hypertension or atherosclerosis, can lead to long-term changes in the mechanical environment surrounding VSMCs. While the changes in matrix mechanics are often included in mechano-adaptation models, the effect of the change in mechanics on VSMC function is not. The principal investigators hypothesize that phenotype switching plays an important measurable role in vascular smooth muscle mechano-adaptation, and that both phenotype and mecahno-adaptation dynamics are influenced by extracellular mechanical properties. They will employ novel in vitro assays to directly measure VSMC mechano-adaptation and use these measurements to develop more in-depth theory for use in models of artery mechanics.