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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

Traction stresses are distributed according to a Burr distribution. Stress distributions for microglia growing on substrates of G′ ~100, ~300, and ~1000 Pa are shown in (A–C), respectively. Red curves represent the best three-parameter Burr distribution fits. (D) The stress distributions were normalized by their standard deviation. Blue curves show the normalized stress distributions for G′ ~100, ~300, and ~1000 Pa, which were statistically similar (p > 0.25, Kruskal-Wallis ANOVA). The red curve shows the Burr distribution fit for all data combined.
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Figure 7: Traction stresses are distributed according to a Burr distribution. Stress distributions for microglia growing on substrates of G′ ~100, ~300, and ~1000 Pa are shown in (A–C), respectively. Red curves represent the best three-parameter Burr distribution fits. (D) The stress distributions were normalized by their standard deviation. Blue curves show the normalized stress distributions for G′ ~100, ~300, and ~1000 Pa, which were statistically similar (p > 0.25, Kruskal-Wallis ANOVA). The red curve shows the Burr distribution fit for all data combined.

Mentions: The distributions of average stresses we found on all substrates (except substrates of 10 kPa, which were excluded because most deformations were below our optical resolution limit) can be well described by a Burr type XII distribution (Figures 7A–C). The probability density function p of the three-parameter Burr distribution is


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)

Traction stresses are distributed according to a Burr distribution. Stress distributions for microglia growing on substrates of G′ ~100, ~300, and ~1000 Pa are shown in (A–C), respectively. Red curves represent the best three-parameter Burr distribution fits. (D) The stress distributions were normalized by their standard deviation. Blue curves show the normalized stress distributions for G′ ~100, ~300, and ~1000 Pa, which were statistically similar (p > 0.25, Kruskal-Wallis ANOVA). The red curve shows the Burr distribution fit for all data combined.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Traction stresses are distributed according to a Burr distribution. Stress distributions for microglia growing on substrates of G′ ~100, ~300, and ~1000 Pa are shown in (A–C), respectively. Red curves represent the best three-parameter Burr distribution fits. (D) The stress distributions were normalized by their standard deviation. Blue curves show the normalized stress distributions for G′ ~100, ~300, and ~1000 Pa, which were statistically similar (p > 0.25, Kruskal-Wallis ANOVA). The red curve shows the Burr distribution fit for all data combined.
Mentions: The distributions of average stresses we found on all substrates (except substrates of 10 kPa, which were excluded because most deformations were below our optical resolution limit) can be well described by a Burr type XII distribution (Figures 7A–C). The probability density function p of the three-parameter Burr distribution is

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