Grant: Project Grant

The movement of cells from one location in the human body to another ("cell migration") is vital for myriad activities to occur both in health and disease states. In vertebrates, cell migration is absolutely critical for positioning cells during development, for wound healing and immune system functioning, but it also drives cancer metastasis and heart diseases. Cell migration is controlled by signals that originate outside the cells including growth factors, cell- generating forces and tissue mechanics. Migration of cancer cells, in particular, depends heavily on mechanical properties, e.g. stiffness, of the microenvironment. However, how cells sense tissue stiffness and then translate this information to control cell migration is not known. The project we propose seeks to identify the specific mechanisms and key players that control cell response to tissue stiffness. We will study how fluctuating forces exerted by cells on the extracellular matrix regulate mechanotransduction and cell migration. We propose changing force dynamics suppresses cell migration towards stiffer tissue, a specific type of cell migration that drives cancer metastasis. This project will shed light on how healthy mammalian cells and cancer cells sense the mechanical properties of the environment. Our results will improve the understanding of how cells migrate in response to mechanical cues. In the long-term, this information will be important to developing drugs that target cell migration in human diseases.