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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

Dependency of the scale parameter α (A) and the traction stress σ (B) on the gel's shear modulus G′. (A) Blue crosses represent α values determined for G′ ~100, ~300, and ~1000 Pa, the black cross represents an α value approximated for G′ ~ 10 kPa using the master curve and the constant peak stress to standard deviation ratio. An initial regime of fast increase of α (which scales proportionally with the median traction stress) was observed for shear moduli below ~2 kPa. The red curve represents the best fit with an adjusted R2-value of 0.99. (B) Boxplots of the traction stresses σ for G′ ~100, ~300, and ~1000 Pa are shown in blue. Black boxplot shows the estimated traction stress σ for G′ ~10 kPa. An initial regime of fast increase of σ was observed for shear moduli below ~2 kPa. The red curve represents the best fit through the median traction stresses with an adjusted R2 value of 0.99.
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Figure 8: Dependency of the scale parameter α (A) and the traction stress σ (B) on the gel's shear modulus G′. (A) Blue crosses represent α values determined for G′ ~100, ~300, and ~1000 Pa, the black cross represents an α value approximated for G′ ~ 10 kPa using the master curve and the constant peak stress to standard deviation ratio. An initial regime of fast increase of α (which scales proportionally with the median traction stress) was observed for shear moduli below ~2 kPa. The red curve represents the best fit with an adjusted R2-value of 0.99. (B) Boxplots of the traction stresses σ for G′ ~100, ~300, and ~1000 Pa are shown in blue. Black boxplot shows the estimated traction stress σ for G′ ~10 kPa. An initial regime of fast increase of σ was observed for shear moduli below ~2 kPa. The red curve represents the best fit through the median traction stresses with an adjusted R2 value of 0.99.

Mentions: Using these results, we can make a prediction on the dependency of the scaling parameter α on the shear modulus G′ of the substrate microglial cells grow on (Figure 8A). This dependency can be described by


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)

Dependency of the scale parameter α (A) and the traction stress σ (B) on the gel's shear modulus G′. (A) Blue crosses represent α values determined for G′ ~100, ~300, and ~1000 Pa, the black cross represents an α value approximated for G′ ~ 10 kPa using the master curve and the constant peak stress to standard deviation ratio. An initial regime of fast increase of α (which scales proportionally with the median traction stress) was observed for shear moduli below ~2 kPa. The red curve represents the best fit with an adjusted R2-value of 0.99. (B) Boxplots of the traction stresses σ for G′ ~100, ~300, and ~1000 Pa are shown in blue. Black boxplot shows the estimated traction stress σ for G′ ~10 kPa. An initial regime of fast increase of σ was observed for shear moduli below ~2 kPa. The red curve represents the best fit through the median traction stresses with an adjusted R2 value of 0.99.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Dependency of the scale parameter α (A) and the traction stress σ (B) on the gel's shear modulus G′. (A) Blue crosses represent α values determined for G′ ~100, ~300, and ~1000 Pa, the black cross represents an α value approximated for G′ ~ 10 kPa using the master curve and the constant peak stress to standard deviation ratio. An initial regime of fast increase of α (which scales proportionally with the median traction stress) was observed for shear moduli below ~2 kPa. The red curve represents the best fit with an adjusted R2-value of 0.99. (B) Boxplots of the traction stresses σ for G′ ~100, ~300, and ~1000 Pa are shown in blue. Black boxplot shows the estimated traction stress σ for G′ ~10 kPa. An initial regime of fast increase of σ was observed for shear moduli below ~2 kPa. The red curve represents the best fit through the median traction stresses with an adjusted R2 value of 0.99.
Mentions: Using these results, we can make a prediction on the dependency of the scaling parameter α on the shear modulus G′ of the substrate microglial cells grow on (Figure 8A). This dependency can be described by

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