title: Microglia mechanics: immune activation alters traction forces and durotaxis.
abstract: 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 ~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.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK ; Faculty of Computer Science and Biomedical Engineering, Institute of Biomechanics, Graz University of Technology Graz, Austria.
authors.forename: Lars
authors.initials: L
authors.lastname: Bollmann
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK ; Department of Physics, Institute for Theoretical Physics, University of Cologne Cologne, Germany.
authors.forename: David E
authors.initials: DE
authors.lastname: Koser
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Shahapure
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK.
authors.forename: Hélène O B
authors.initials: HO
authors.lastname: Gautier
authors.affiliation: Faculty of Computer Science and Biomedical Engineering, Institute of Biomechanics, Graz University of Technology Graz, Austria.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Holzapfel
authors.affiliation: Fischell Department of Bioengineering, University of Maryland College Park, MD, USA.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Scarcelli
authors.affiliation: Scottish Universities Physics Alliance (SUPA), School of Physics and Astronomy, University of St Andrews St Andrews, UK.
authors.forename: Malte C
authors.initials: MC
authors.lastname: Gather
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK.
authors.forename: Elke
authors.initials: E
authors.lastname: Ulbricht
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, UK.
authors.forename: Kristian
authors.initials: K
authors.lastname: Franze
keywords: CNS; LPS; biased random walk; foreign body reaction; gliosis; mechanotaxis; migration; random walk