Using video force microscopy (VFM) to determine the forces that drive morphogenetic movements of cells and tissues

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Most people do not realize how important cell and tissue movements are to human health. However, it is through such movements that organs and other critical structures form during early embryo development, that wounds heal, that cells leave a primary cancer tumour and establish metastases, and that proper structure and function arise in engineered tissues. These movements are driven by sub-cellular structural components, and alterations to the forces they generate can significantly impact health outcomes. One could conceive pharmaceutical and other means to therapeutically manipulate these forces, but we must have practical ways to measure them if we are to evaluate proposed interventions, and that is the goal of my research program. My research team recently invented a way to determine the forces at work in cells and tissues from time lapse movies of their motions. When this new computational modeling technique, called video force microscopy (VFM), was used to investigate ventral furrow formation in Drosophila (fruit fly) embryos, it made it possible to map the forces acting in individual cells and to track how these forces change with time. This new knowledge explained why some embryos develop normally while others acquire birth defects. Discovery Grant funding is needed so that my team can address mathematical and mechanical issues that limit the reliability and general applicability of this promising technique. For example, if cells in mono-layer sheets are driven simultaneously by contractions along their edges and top surfaces, our current VFM algorithms can have difficulty distinguishing the contributions of each. We want to resolve these issues and use VFM to study wound healing and other important cell and tissue movements. We hope that VFM will become a standard tool for the study of cell and tissue mechanics, and we hope that it will lead to improved strategies for prevention of birth defects and cancer metastasis and give rise to new approaches in tissue engineering.