Computational Biomechanics Modeling of Inflammation

Project Summary/Abstract The physical laws that govern the universe also govern the healthy functioning of living tissues, as well as the genesis and development of diseases. Historically, the biomedical research community has overlooked the role of mechanics in many developmental, pathological, and adaptive processes. In my research group, the Compu- tational Mechanics of Morphology at Notre Dame (CoMMaND Lab), we work at the intersection of mechanics, computation, and biology, to investigate the coupled bio-mechanical behaviors of tissues and organs, particularly during growth and remodeling. In this proposal, we aim to extend our work to the study of inflammatory swelling. Similarly to growth, inflammation and swelling involve local changes in mass (for instance, due to an influx of cells) which can manifest as changes in volume. While external swelling is often used as an indicator of under- lying inflammation, constraints from surrounding tissue can also restrict swelling and instead result in increases in pressure. In addition, inflammation can drastically change the cellular composition of a tissue. Inflammation is widespread among different tissues, and these sequelae can have important implications for the diagnosis, de- velopment, and treatment of different diseases. We will developing novel computational models of inflammation and swelling that 1) allow for cell behavior to vary spatially, temporally, and by cell type; 2) account for mechanical interactions between the swelling tissue and surrounding tissues; and 3) report results in a way that facilitates calibration, validation, and comparisons with experimental. This work will provide tools for probing small-scale phenomena beyond large-scale swelling, exploring the effects of individual parameters, and testing hypotheses regarding the biomechanics of inflammation in silico. 1