Regensburg 2016 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 37: Cell Mechanics and Migration
BP 37.2: Vortrag
Mittwoch, 9. März 2016, 10:00–10:15, H44
Microglia mechanics: From traction forces to durotaxis — •David Koser1,2, Lars Bollmann1, and Kristian Franze1 — 1University of Cambridge, Cambridge, United Kingdom — 2German Cancer Research Center, Heidelberg, Germany
Microglial cells are key players in the primary immune response of the central nervous system. Their functionality in healthy and pathological conditions highly depends on their chemical as well as their mechanical environment. While the impact of chemical signaling on microglial behavior has been studied thoroughly, the current understanding of mechanical signaling in controlling the cells' behavior is very limited. Here we investigated the dependency of microglial traction forces on substrate stiffness and the cells' migratory behavior on substrates incorporating stiffness gradients. Primary microglia adapted their actin cytoskeleton and morphology to the stiffness of the culturing substrate. Traction force microscopy revealed that stresses exerted by the cells initially increase with substrate stiffness until reaching a plateau. On substrates incorporating a stiffness gradient microglial cells preferentially migrated towards stiff in a process termed durotaxis. Immune-activation of microglia through lipopolysaccharide led to a modulation of traction forces, increased migration velocities, and an enhancement of durotaxis. Finally, the experimental findings can be reproduced by combining a phenomenological stress fluctuation and a biased random walk model. Our results clearly demonstrate that microglia are mechanosensitive, which might be essential in central nervous system development and pathologies.