7th Annual Symposium
Physics of Cancer
October 4-6, 2016
|PoC - Physics of Cancer - Annual Symposium|
Mechanical aspects of angiogenesis
Ludwig-Maximilians-University Munich, Pharmaceutical Biology, Center for Drug Research, Butenandtstr. 5-13, 81377 Munich
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In order to evade logistic limits of growth set by supply with oxygen and nutrients, tumors have to organize a vascular system of their own. This process of vascularization is termed angiogenesis, and has become an integral target of current cancer therapy. The underlying mechanisms of cell behavior and pattern formation have, to date, mainly been investigated on a biochemical level, not in terms of mechanotransduction.
Using microstructured surfaces, we dissected the specific roles of cell shape, adhesion surface, cell-cell contacts and dynamical changes for the activation of the mechanosensitive transcription regulators MRTF and YAP. Adhesion surface and cell-cell contacts turned out to be the major regulators for the activity of both signaling pathways, while cell shape played no role. Both transcription factors responded quickly (within minutes). Dynamic studies showed that MRTF is also quickly de-activated, while YAP responds much slower. This indicates that the two mechanosensitive pathways are not just redundant, but serve different purposes (quick response vs. sustained activation).
In a second setup we investigated the role of forces for vascular pattern formation. We found that the initial finding process between cells is not necessarily induced by chemotactic gradients, but depends on mechanical communication by matrix deformation. This communication turned out to crucially depend on the biophysical properties of the matrix (stiffness, topography).