Metastability of Cell Migration Polarity

North Carolina State University, Raleigh NC

Investigators

Abstract

The overall goal of the proposed project is to elucidate the fundamental physical mechanisms governing the reorientation of cell migration polarity, which affects how persistently the cells maintain their directionality of movement and their ability to follow spatial cues during physiological processes such as wound healing, the immune response, and embryonic development. The phosphoinositide 3-kinase (PI3K) signaling pathway has been implicated in the control of cell reorientation, which is achieved by stabilizing the branching of existing cell protrusions activity. Using an approach integrating live-cell fluorescence microscopy, image analysis, and computational modeling, the team will characterize and manipulate the dynamics of signal transduction pathways, focal adhesions, and the actin cytoskeleton during protrusion branching. The hallmarks of cell reorientation thusly identified will be re-evaluated in PI3K-inhibited cells to evaluate if the dynamics are altered and how. These research objectives are to be integrated with educational activities, and, through the support and training of graduate students and the participation of undergraduate students, the project will contribute to the training of researchers in the cross-disciplinary areas of engineering analysis and cell biology.