Regensburg 2010 – scientific programme
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BP: Fachverband Biologische Physik
BP 15: Physics of Cells II
BP 15.7: Talk
Tuesday, March 23, 2010, 16:15–16:30, H43
The role of the G protein-coupled receptor CXCR4 in angiogenesis - a single-molecule approach — •Susanne Fenz1, Cassandra Verheul1, Ewa Snaar-Jagalska2, and Thomas Schmidt1 — 1Leiden Institute of Physics, Leiden, The Netherlands — 2Institute of Biology, Leiden, The Netherlands
Directed cell movement in a chemical gradient, chemotaxis, is a prerequisite for many vital processes like the immune response, but it is also the basis for cancer metastasis. Chemotaxis is governed by extracellular gradients of small molecules, the chemokines. While their receptors in the cell membrane are identified, it is still unknown how the cell subsequently builds up an asymmetric phenotype with defined front and rear edge, necessary for directed movement. This polarization is triggered by tiny gradients and is robust in noisy environment. Thus, we propose that universal physical mechanisms underlie the first steps towards polarity.
Two potential ordering parameters, the receptor mobility and cytoskeleton-induced membrane domains, were investigated on a molecular level in living mouse fibroblasts and human vascular endothelial cells. We applied single-molecule fluorescence microscopy to characterize the diffusion behaviour of CXCR4-eYFP upon stimulation with its chemokine SDF and to probe for potential association with CCR5. Since it is known that tumor cells expressing CXCR4 perform metastasis not only by direct migration to organs expressing SDF, but additionally promote angiogenesis towards the tumor our model system will yields insights into both mechanisms.