Structure-Based Mechanical Modeling of Basement Membrane

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DESCRIPTION (provided by applicant): Basement membranes are ubiquitous and essential, serving as the scaffold for numerous and important endothelial, epithelial and excitable tissues. Because of their importance, basement membranes are extremely well studied. Although experimental studies have yielded much information about the composition and biology of basement membranes, the details of their assembly and structure remain elusive. In this work, we propose a novel approach to explore basement membrane structure, using advanced computational methods to provide a bridge between hypotheses about basement membrane architecture and experimental measurements of basement membrane behavior. The method will be implemented on a series of increasingly-complex models of the type IV collagen network in the basement membrane, and a multi-scale modeling scheme will be used to predict macroscopic behavior based on the microscopic structure. In keeping with the focused, exploratory mission of the R21 program, our goal is to implement the proposed scheme and assess whether it is feasible as a research tool. This project relates directly to public health because insight into structure and function of basement membranes can provide insight into organ function and disease treatment. Furthermore, principles established in the proposed studies can inform the development of biomaterials for medical applications. This project relates directly to public health because insight into structure and function of basement membranes can provide insight into organ function and disease treatment. Furthermore, principles established in the proposed studies can inform the development of biomaterials for medical applications.