Phase Field modeling to track and predict heterogeneous cell cluster migration in response to dynamic chemoattractant distribution

During animal development and wound healing, cells of the body must migrate to new locations in a coordinated way. If this goes wrong, it could lead to abnormal embryo development or failure of injury repair. Moving cells, which often move as a group, rely on chemicals in their environment to direct them to the correct location. The proposed project will produce a representation of how a cluster of cells move in a live organism, which will provide insight on how they coordinate movements and interpret dynamic signals in their specific area. Using genetics and live-imaging data, mechanisms of migration will be captured in a computationally efficient framework that accurately reflects the normal tissue and can track individual cell behaviors that create group movements, which will have broad applications to many multicellular processes. The framework will be further advanced to include the dynamics of developing tissue. Participants in the project will gain experience in a collaborative, interdisciplinary training environment that bridges math and biology to provide valuable biotechnology research opportunities for trainees across a span of levels and across disciplines. Clustered cell migration in the Drosophila (fruit fly) ovary provides a powerful system for identifying molecular and biophysical components that govern this process generally. The fly ovary is amenable to a combination of modeling, genetics, and advanced imaging of living tissues, making it largely unparalleled to other platforms but adept at uncovering general principles. This project takes to the next level a recent hybrid mathematical Reaction Diffusion–Phase Field Model (RD-PFM) framework created to capture chemoattractant distribution and resultant cell migration dynamics. This framework lacked feedback onto chemoattractant distribution, individual cell behaviors, and a third dimension. To understand border cell migration more precisely, this project will first accurately capture the high-dimensional structure of the tissue through which the cells move, the egg chamber. Using high-resolution four-dimensional microscopy data including time, workflow will be developed to analyze and extract the data in a way meaningful for model comparison The methods will be refined to manage the increase in numerical complexity to address: What are the critical characteristics of individual cells observed from live imaging data, how do they contribute to cluster behaviors, and how does the updated model lead to predictions in migration in normal Drosophila and mutant cases in four dimensions? Leveraging preliminary results as a numerically efficient testbed for integrating chemical dynamics with membrane motion, RD-PFM coupling will be implemented to provide a generalizable model for cell migration in dynamic environments. 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.