Many cells exist in dynamic mechanical environments, necessitating constant adaptation to maintain tissue integrity. Biomechanical models can provide mechanistic insight into these adaptive processes and, if robust enough, could assist in physicians' treatment decisions. Our lab focuses on developing in vitro experimental methods and computational tools necessary to advance our understanding of cell-scale and tissue-scale mechanobiology and develop clinically-applicable mathematical models.
Nonlinear Cellular Mechanics. Most tissues are mechanically anisotropic and nonlinear at large strains. However, though cells within tissues have highly organized structures and undergo similar strains to the tissues they are a part of, cellular properties are normally reported as linear moduli. To understand how mechanical forces alter cellular behavior, it is necessary to describe the full material behavior of cells. We are developing in vitro methods for characterizing aniostropic hyperelastic and viscoelastic constitutive behavior of cells, determining how those properties can be altered, and elucidating the role of adaptive property modulation in disease progression.
Mechano-Transduction and Mechano-Adaptation. In development and disease, mechanical forces drive morphological and functional changes in cells and tissues. During development morphogenetic forces drive tissue and organ formation through mechano-adaptive pathways. In disease, mechano-adaptation can be functional, as in hypertension, where stress-induced arterial growth and remodeling leads to stiffer and thicker vessels, lowering the wall stress, or dysfunctional, as in aneurysm growth or vasospasm, where these same mechano-adaptive processes can lead to long-term deleterious results. Using a combined in vitro/in silico approach, we aim to elucidate both the phenomenological behavior and mechanistic underpinnings of cell response to altered mechanical environment.
Neurotrauma. Traumatic brain injury affects millions of people each year, from athletes and car accident victims exposed to blunt force trauma to soldiers exposed to explosive blasts. Macroscopic forces from impacts or blasts are ultimately sensed at the cellular level and pathologically transduced, leading to clinical complications ranging from short-term concussions to early-onset Alzheimer's disease. We are developing in vitro models to determine how both trauma-like mechanical loads and secondary effects of injury affect cellular function in neurons, glia, and cerebral vasculature.