Dresden 2011 – scientific programme
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BP: Fachverband Biologische Physik
BP 15: Single-Molecule Biophysics I
BP 15.8: Talk
Tuesday, March 15, 2011, 12:30–12:45, ZEU 250
CXCR4-SDF1 mediated chemotaxis on the single molecule level — •Susanne Fenz1, Cassandra Verheul1, Ewa Snaar-Jagalska2, and Thomas Schmidt1 — 1Leiden Institute of Physics, Leiden University, The Netherlands — 2Leiden Institute of Biology, Leiden University, The Netherlands
Directed cell movement in a chemical gradient, chemotaxis, is not only a prerequisite for many vital processes like the immune response, but also the basis for cancer spreading in metastasis. Chemotaxis is governed by extracellular gradients of small molecules, the chemokines. The receptor CXCR4 and its chemokine SDF1 play a crucial role in directing migration of tumor cells to neighbouring tissue as well as in metastasis to distant sites in the body. Two potential ordering parameters, the receptor mobility and cytoskeleton-induced membrane domains, were investigated on a molecular level in living fibroblasts and endothelial cells. We applied single-molecule fluorescence microscopy to characterize the diffusion behaviour of CXCR4-eYFP in resting cells and upon stimulation with SDF1. Particle Image Correlation Spectroscopy yields two fractions of receptors prior to stimulation: half of the receptors are immobile while the other half exhibits free diffusion with D = 0.3 mum2/s on short timescales (up to 100 ms). At longer timescales the receptors show confined diffusion within micrometer domains. Global stimulation with SDF1 switches a subset of the receptors from the immobile to the mobile fraction. We hypothesize that the impact of a gradient of SDF-1 might lead to asymmetric receptor diffusion and subsequently polarized cell behavior.