In vitro system for exploring cellular force transmission during angiogenesis.

Organ function is dependent on the formation of a functional blood circulatory network. Angiogenesis is the process of forming new blood capillaries from pre-existing ones, where endothelial cells (ECs) residing on capillary walls invade the surrounding extracellular matrix (ECM) and form angiogenic sprouts. Cell invasion is strongly dependent on the ability of cells to generate traction forces, rendering traction generation fundamental to angiogenesis. However, how mechanical forces are generated by ECs and how this is important for vascular invasion is still poorly understood, among others because so far no one has ever quantified tractions during angiogenesis. For that reason, the main goal of this project is to develop a versatile in vitro system in which cellular forces generated during angiogenesis can be investigated in a controlled fashion, by combining computational modelling with state of the art microfluidics and optical microscopy. This system will be used to explore fundamental research questions on the effect of ECM mechanical properties on the generation of cellular forces, the role of a specific protein called angiomotin (Amot) in force transmission from the ECM to the nucleus, and how this affects angiogenesis. The study of the role of the nucleus is a particularly novel aspect and may lead to novel findings on the way cellular forces regulate angiogenesis through their mechanical effect on the nucleus