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Microglia mechanics: immune activation alters traction forces and durotaxis.

Bollmann L, Koser DE, Shahapure R, Gautier HO, Holzapfel GA, Scarcelli G, Gather MC, Ulbricht E, Franze K - Front Cell Neurosci (2015)

Bottom Line: 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.Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Microglia spread area as a function of substrate stiffness. The spread area of microglial cells significantly increased with substrate stiffness (p < 0.05, Kruskal-Wallis ANOVA; for G′ ~ 100 Pa vs. 1 kPa, p < 0.01, Mann-Whitney U-test). **p < 0.01.
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Figure 1: Microglia spread area as a function of substrate stiffness. The spread area of microglial cells significantly increased with substrate stiffness (p < 0.05, Kruskal-Wallis ANOVA; for G′ ~ 100 Pa vs. 1 kPa, p < 0.01, Mann-Whitney U-test). **p < 0.01.

Mentions: To investigate how microglia mechanically interact with their environment, we first investigated how their morphology changes with substrate stiffness. Primary microglial cells were cultured on soft, elastic substrates made of polyacrylamide with shear moduli G′ of 100, 300, and 1000 Pa, spanning the range of reported neural tissue stiffness (Franze et al., 2013). The spread area of primary microglial cells significantly increased with substrate stiffness (p < 0.05, Kruskal-Wallis ANOVA) (Figure 1). The median cell spread area increased from 112 μm2 on soft substrates (G′ ~ 100 Pa), to 163 μm2 on stiff substrates (G′ ~ 1000 Pa) (p < 0.01, Mann-Whitney U-test).


Microglia mechanics: immune activation alters traction forces and durotaxis.

Bollmann L, Koser DE, Shahapure R, Gautier HO, Holzapfel GA, Scarcelli G, Gather MC, Ulbricht E, Franze K - Front Cell Neurosci (2015)

Microglia spread area as a function of substrate stiffness. The spread area of microglial cells significantly increased with substrate stiffness (p < 0.05, Kruskal-Wallis ANOVA; for G′ ~ 100 Pa vs. 1 kPa, p < 0.01, Mann-Whitney U-test). **p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585148&req=5

Figure 1: Microglia spread area as a function of substrate stiffness. The spread area of microglial cells significantly increased with substrate stiffness (p < 0.05, Kruskal-Wallis ANOVA; for G′ ~ 100 Pa vs. 1 kPa, p < 0.01, Mann-Whitney U-test). **p < 0.01.
Mentions: To investigate how microglia mechanically interact with their environment, we first investigated how their morphology changes with substrate stiffness. Primary microglial cells were cultured on soft, elastic substrates made of polyacrylamide with shear moduli G′ of 100, 300, and 1000 Pa, spanning the range of reported neural tissue stiffness (Franze et al., 2013). The spread area of primary microglial cells significantly increased with substrate stiffness (p < 0.05, Kruskal-Wallis ANOVA) (Figure 1). The median cell spread area increased from 112 μm2 on soft substrates (G′ ~ 100 Pa), to 163 μm2 on stiff substrates (G′ ~ 1000 Pa) (p < 0.01, Mann-Whitney U-test).

Bottom Line: 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.Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus