Combining Genetic and Mechanical Factors to Model Disease

Abstract

To study the origin of disease, which is complicated by patient-to-patient variability and tissue heterogeneity, it is necessary to study the root causes of both extrinsic and intrinsic mechanisms. While extrinsic factors are generally obvious for diseases, e.g. diet and exercise, intrinsic ones are less so, e.g. genetics or environmentally induced genetic stimuli. This chapter first summarizes recent work investigating the effect of inherited genetic risk using examples from cardiovascular disease and cancer and technologies such as iPSCs and/or gene editing. Second, we summarize recent advancements in materials-based mechanobiology in which mechanical stimuli, whether from the ECM, surrounding fluid, or neighboring cells, were modulated to study their role in disease. Finally, instances where both genetics and mechanics are jointly manipulated to model disease are discussed. Most genetic risk acts through unknown mechanisms; however, we propose future systematic study of these effects in combination to uncover novel mechanisms that would otherwise be missed if modeled separately.