Force transmission through cell-cell and cell-matrix interactions in a bilayered epithelium during wound healing

The National Institute of Child Health and Human Development awarded New York University $100,228 on January 1, 2027, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to support research on force transmission through cell-cell and cell-matrix interactions in bilayered epithelia during wound healing.

The research uses embryonic zebrafish skin as a genetically tractable two-layered epithelium to define the roles of cell-cell and cell-matrix adhesions in coordinating forces during wound closure. The experimental design combines protein depletion in a tissue-specific manner with in vivo traction force measurement to link molecular mechanisms to mechanical outputs necessary for wound closure. The work aims to provide comprehensive understanding of wound closure in vivo to inform therapeutic strategies for chronic wounds.

NYU School of Medicine is the recipient, performing work at New York, NY 10016. The period of performance runs from January 1, 2027, through August 31, 2031. The assistance type is a Project Grant.

Abstract

Wound healing requires the collective migration of cells to close gaps in tissues and maintain barrier function. Prior studies using single-layered epithelia demonstrated that during wound closure, tissues generate forward- moving forces by deforming the underlying matrix. In the skin, the underlying matrix is the basement membrane, a specialized extracellular matrix that anchors the epithelium. However, IT is unclear how multilayered epithelia like the skin close wounds given their native basement membrane composition and complex interactions. This proposal aims to define the roles of cell-cell and cell-matrix adhesions in coordinating forces in a multilayered epithelium during wound closure. IT utilizes the embryonic zebrafish skin as genetically tractable two-layered epithelium suitable for live imaging. Additionally, the proposed experimental design combines a novel tool to deplete proteins in a tissue-specific manner, with a method to measure traction forces in vivo. Together, these methods offer a powerful way to link molecular mechanisms to mechanical outputs that are necessary for wound closure. Ultimately, this research aims to provide a comprehensive understanding of wound closure in vivo, informing therapeutic strategies for diseases featuring chronic wounds.