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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 activation through LPS changes traction stresses. After 5 min incubation in LPS, (A) peak traction stresses and (B) average traction stresses decreased on stiffer substrates (G′ ~ 300 or 1000 Pa) but slightly increased on soft gels of G′ ~ 100 Pa (shown is the mean ± SEM).
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Figure 5: Microglia activation through LPS changes traction stresses. After 5 min incubation in LPS, (A) peak traction stresses and (B) average traction stresses decreased on stiffer substrates (G′ ~ 300 or 1000 Pa) but slightly increased on soft gels of G′ ~ 100 Pa (shown is the mean ± SEM).

Mentions: After incubation in LPS-containing medium for ~5 min, we found a trend for traction forces to decrease within 10 min on stiffer substrates (1000 Pa and 300 Pa) and to increase slightly on 100 Pa gels (Figure 5). Testing if the slopes of the peak traction stresses over time significantly differed from 0 yielded a p-value of 0.06 at 1 kPa (one sample t-test); for all other conditions p > 0.06. Investigating the dependence of peak and average traction stresses on substrate stiffness and 10–15 min LPS treatment revealed interaction p-values of 0.002 and 0.004 (Two-Way ANOVA), respectively, indicating that the substrate stiffness-dependent traction forces significantly changed when microglia were activated by LPS.


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 activation through LPS changes traction stresses. After 5 min incubation in LPS, (A) peak traction stresses and (B) average traction stresses decreased on stiffer substrates (G′ ~ 300 or 1000 Pa) but slightly increased on soft gels of G′ ~ 100 Pa (shown is the mean ± SEM).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Microglia activation through LPS changes traction stresses. After 5 min incubation in LPS, (A) peak traction stresses and (B) average traction stresses decreased on stiffer substrates (G′ ~ 300 or 1000 Pa) but slightly increased on soft gels of G′ ~ 100 Pa (shown is the mean ± SEM).
Mentions: After incubation in LPS-containing medium for ~5 min, we found a trend for traction forces to decrease within 10 min on stiffer substrates (1000 Pa and 300 Pa) and to increase slightly on 100 Pa gels (Figure 5). Testing if the slopes of the peak traction stresses over time significantly differed from 0 yielded a p-value of 0.06 at 1 kPa (one sample t-test); for all other conditions p > 0.06. Investigating the dependence of peak and average traction stresses on substrate stiffness and 10–15 min LPS treatment revealed interaction p-values of 0.002 and 0.004 (Two-Way ANOVA), respectively, indicating that the substrate stiffness-dependent traction forces significantly changed when microglia were activated by LPS.

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