The research objective of this NSF Faculty Early Career Development (CAREER) Program award is to understand how cells move across tissue of varying stiffness to reach distant locations within the body. The ability of cells to move, both singly and together, through living tissue fundamentally controls how our bodies function in health and disease, including development, aging, and disorders such as cancer. Throughout their life cycle, cells move in time and space according to a complex program. While various steps of this process have been studied separately, it is not well understood if multiple steps of the cell migration process are interdependent. This research will tackle these unanswered questions through an innovative multi-disciplinary approach that combines micro-fabrication, biomaterials, cell biology, and computer simulation. These studies will reveal how mechanical properties of the tissue regulate how cells move, both as individuals and groups, which in turn will help create new strategies to engineer cell motion. These research efforts will be combined with an education and outreach plan to develop a framework for training and educating graduate, undergraduate, and K-12 students at the interface of engineering and biology.
The knowledge about time and length scales of changes in cellular phenotypes across heterogeneous environments might enable better predictions of how cells invade complex tissue. Towards this research goal, the project will employ engineering-based approaches that allow systematic "time and space" deconstruction of intra- and extra-cellular parameters. These studies will include fabrication of tissue-mimetic cell culture platforms of tunable mechanical properties, study of cell motility across matrices of varying properties, and construction of computational models simulating single and collective cell migration in diverse environments. The accompanied education plan highlights how engineering-based approaches are often uniquely suited to study complex biological processes. The education activities will train students in cellular mechanobiology through an integrated community outreach program consisting of a robotic cell-crawling exhibit and corresponding teaching modules for high-school students. The computer simulations and cell motility videos from research efforts will be included in the teaching modules and made available to science teachers from partner high schools. The education plan also includes undergraduate and graduate course development on "mechanics of cell motility" and undergraduate research internships for first year students to encourage multidisciplinary learning at an early stage.
