EAPSI: Integrating mechanical and biochemical cues in wound healing

Schrier Sarah, Cambridge MA

Investigators

Abstract

A fundamental question in biology is how cells can maintain their cell-cell contacts and move together in two-dimensional and three-dimensional space. This process is important in functions including tissue development, wound healing, and invasion of tumor cells. While there is considerable knowledge about how single cells migrate, little is known about how groups of cells migrate together. Many researchers have looked into individual molecules that contribute to the ability of cells to migrate collectively, but investigations into the role of the mechanical properties of the environment are still in early stages. In collaboration with Dr. Paul Matsudaira, of the National University of Singapore, this study will use substrates with different mechanical properties to investigate how these mechanical cues mimicking physiological environments, for example stiffness, effect collective cell migration. The Mechanobiology Institute at the National University of Singapore has state of the art instrumentation and expertise that will enable the completion of this study. More specifically, this project will use a tunable viscoelastic substrate to investigate how mechanical cues from the environment affect collective cell migration. The balance between cell-matrix adhesions and cell-cell adhesion will be studied by looking into the biochemical properties that mediate substrate induced collective cell migration. Single-cell confocal and fluorescence imaging will be employed, along with development of automated image-processing tools, to quantitatively assess cell-junctions in real time migration experiments. Modulating biochemical factors known to be important in collective cell migration (including focal adhesion kinase, proteases, and cadherins) will be used to uncover mechanisms that differ between stiff and viscous substrate migration to develop a more complete model of how epithelial cells make collective decisions in response to their environment. The successful completion of this project will result in a more concrete understanding of tissue migration and dynamics in physiological environments. This NSF EAPSI award is funded in collaboration with the National Research Foundation of Singapore.