Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2015.00363
Keywords
migration; mechanotaxis; foreign body reaction; random walk; LPS; CNS; gliosis; biased random walk
Categories
Funding
- Austrian Agency for International Cooperation in Education and Research
- Faculty of Computer Science and Biomedical Engineering at Graz University of Technology
- German National Academic Foundation
- Wellcome Trust/University of Cambridge Institutional Strategic Support Fund
- Isaac Newton Trust [14.07]
- Leverhulme Trust [RPG-2014-217]
- UK Medical Research Council
- Human Frontier Science Program [RGY0074/2013]
- MRC [G1100312] Funding Source: UKRI
- Medical Research Council [G1100312] Funding Source: researchfish
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Microglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of similar to 5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning.
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