This Faculty Early Career Development (CAREER) grant will enable the comprehensive study of coordinated cell behavior. Coordinated cell behavior is a hallmark of both organism development and organism functioning. Collective cell migration is one example of such cellular coordination. It plays a central role in embryonic development, wound healing, and cancer invasion. Despite its importance, collective cell migration is poorly understood. Studying coordinated cell movement is challenging because the processes that regulate cellular machinery, the interaction of cells with each other, and their interaction with their local environment all affect each other. The research community lacks tools that can grasp such complexity at the systems level. This work will overcome this challenge by integrating state-of-the-art imaging technologies with comprehensive simulation models of cellular dynamics that bridge different length and time scales. This will reveal how the complex interplay of cell responses defines the emergent collective behavior. Beyond the research laboratory, the results of the work and enthusiasm for research will be broadcast widely through outreach efforts, launching the career of the Principal Investigator. Specifically, the project will benefit the society by introducing project-related, inclusion-focused undergraduate and graduate courses and a STEM Diversity Internship for underrepresented students from Spelman College and K-12 teachers participating in the Georgia Tech GIFT Program.
The specific goal of the project is to decipher complex cross-talk mechanisms between the environment-dependent cell signaling and the cytoskeletal machinery via the implementation of a novel, hybrid (agent-based/systems-dynamics) method. This method explicitly accounts for the spatiotemporal regulation of actin and adhesion complexes, changes in cell shape, and the formation of mechanical stresses. To inform the models and validate their predictions, quantitative experimental characterization of individual and collective cell migration will be carried out using micro-patterned adhesive assays. These assays provide well-controlled extracellular conditions and visualization of different modes of cell migration with high spatial and temporal resolution. This integrative approach will test the project’s central hypothesis that the bidirectional feedback between cell shape, localization of actin regulators, adhesion turnover, and arrangement of stress fibers, predictably determine the mode of migration a cell adopts, ultimately impacting the efficiency of the collective cell migration. Although this project is driven by specific biological hypotheses, the outcome of the effort will be a general, broadly applicable computational methodology for addressing many fundamental questions of cell function in different biological contexts.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
