CAMVAS · Coordination And Migration of Cells during 3D Vasculogenesis

Cell migration is the core of myriad of phenomena in health and disease. Physical forces exerted during collective cellular motion trigger structural adaptations and signaling events that are of paramount importance in tissue engineering, stem cell differentiation and cancer. A spectacular example of coordinated movements towards a useful endpoint is vasculogenesis, the formation ""de novo"" of a network of vessels and capillaries from dispersed endothelial cells. In tissue engineering, precise control of the process of vasculogenesis is essential to create 3D tissue constructs with a proper nutrient and oxygen availability. Such control will only be possible with a deep understanding of cell-cell and cell-matrix mechanical interactions, and biochemical guidance of migrating cells during early 3D vasculogenesis. Providing a theoretical model, experimentally validated, of such multicellular self-organization would highly help in modulating the final architecture of the vascular network. In this project microfluidic experiments are proposed to engineer vasculogenesis within 3D gel matrices, mimicking the native cell environment. The expertise of the outgoing host on microfluidics will ensure the experimental control of chemical and mechanical factors coupled with image acquisition. A continuum-discrete multiscale model, tuned to reproduce mechano-chemical guidance of collectives of cells will be developed in parallel. Measurements of cell-matrix tractions in 3D will be performed at the European host for further mechanical characterization. Traction measurements will be coupled with microfluidics to provide in vitro observations at a high spatiotemporal resolution and extensively validate the in silico model. While advancing the control of 3D vasculogenesis, the project will generate precious knowledge and innovative methodologies that will benefit European research on stem cell mechanobiology during tissue regeneration and in the future, cancer research.""