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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

Microglial cells exert larger forces on stiffer substrates. (A) Average and peak traction stress as a function of time for two representative cells on gels of G′ ~100 Pa and ~1000 Pa. Traction stresses fluctuate over time. (B) Peak traction stress and (C) average traction stress as a function of substrate stiffness G′. Average traction stress values for a substrate stiffness of G′ ~ 10 kPa were excluded because most deformations were below our optical resolution limit. N: number of analyzed cells. **p < 0.01; ***p < 0.001.
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Figure 4: Microglial cells exert larger forces on stiffer substrates. (A) Average and peak traction stress as a function of time for two representative cells on gels of G′ ~100 Pa and ~1000 Pa. Traction stresses fluctuate over time. (B) Peak traction stress and (C) average traction stress as a function of substrate stiffness G′. Average traction stress values for a substrate stiffness of G′ ~ 10 kPa were excluded because most deformations were below our optical resolution limit. N: number of analyzed cells. **p < 0.01; ***p < 0.001.

Mentions: The traction stress (force per unit area) exerted by individual microglial cells, which is responsible for the observed substrate deformations, showed fluctuations over time (Figure 4A), indicating that force generation is a dynamic process. We did not find any distinct traction stress patterns as a function of substrate stiffness (Supplementary Figure 2). Peak as well as average traction stresses exerted by microglial cells changed significantly with substrate stiffness (p < 10−12, Kruskal-Wallis ANOVA and p < 10−14, One-Way ANOVA, respectively). Within the investigated range, traction forces increased with substrate stiffness (p < 0.01 for all comparisons, Mann-Whitney U-test) (Figures 4B,C).


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)

Microglial cells exert larger forces on stiffer substrates. (A) Average and peak traction stress as a function of time for two representative cells on gels of G′ ~100 Pa and ~1000 Pa. Traction stresses fluctuate over time. (B) Peak traction stress and (C) average traction stress as a function of substrate stiffness G′. Average traction stress values for a substrate stiffness of G′ ~ 10 kPa were excluded because most deformations were below our optical resolution limit. N: number of analyzed cells. **p < 0.01; ***p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Microglial cells exert larger forces on stiffer substrates. (A) Average and peak traction stress as a function of time for two representative cells on gels of G′ ~100 Pa and ~1000 Pa. Traction stresses fluctuate over time. (B) Peak traction stress and (C) average traction stress as a function of substrate stiffness G′. Average traction stress values for a substrate stiffness of G′ ~ 10 kPa were excluded because most deformations were below our optical resolution limit. N: number of analyzed cells. **p < 0.01; ***p < 0.001.
Mentions: The traction stress (force per unit area) exerted by individual microglial cells, which is responsible for the observed substrate deformations, showed fluctuations over time (Figure 4A), indicating that force generation is a dynamic process. We did not find any distinct traction stress patterns as a function of substrate stiffness (Supplementary Figure 2). Peak as well as average traction stresses exerted by microglial cells changed significantly with substrate stiffness (p < 10−12, Kruskal-Wallis ANOVA and p < 10−14, One-Way ANOVA, respectively). Within the investigated range, traction forces increased with substrate stiffness (p < 0.01 for all comparisons, Mann-Whitney U-test) (Figures 4B,C).

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