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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 morphology depends on substrate stiffness. (A–D) Representative fluorescence images of microglial cells on substrates of different stiffness. F-actin appears in green, nuclei in blue. (A) On substrates of G′ ~ 100 Pa, microglial cells showed many filopodia-like processes (red arrows). (B) On stiffer substrates (G′ ~ 300 Pa), they showed amoeboid morphologies (red arrow) with significantly fewer processes (p < 0.05, Mann-Whitney U-test). (C,D) On 1000 Pa substrates and on glass, microglial cells had complex morphologies with lamellipodia-like structures at the tips of long processes (red arrows). Scale bar: 10 μm.
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Figure 2: Microglia morphology depends on substrate stiffness. (A–D) Representative fluorescence images of microglial cells on substrates of different stiffness. F-actin appears in green, nuclei in blue. (A) On substrates of G′ ~ 100 Pa, microglial cells showed many filopodia-like processes (red arrows). (B) On stiffer substrates (G′ ~ 300 Pa), they showed amoeboid morphologies (red arrow) with significantly fewer processes (p < 0.05, Mann-Whitney U-test). (C,D) On 1000 Pa substrates and on glass, microglial cells had complex morphologies with lamellipodia-like structures at the tips of long processes (red arrows). Scale bar: 10 μm.

Mentions: After 12 h in vitro, microglia cultured on 100 Pa substrates showed many actin-rich filopodia-like processes (44 ± 3, average ± SEM, n = 14) (Figure 2A). Microglial cells on substrates of G′~300 Pa appeared in a more round or amoeboid shape (Figure 2B), with fewer processes than on softer substrates (24 ± 6, n = 5; p < 0.05, Mann-Whitney U-test). Furthermore, F-actin was distributed more homogeneously throughout the cells. The shape of microglia changed drastically when cultured on 1 kPa substrates or on glass (Figures 2C,D). Cells possessed more complex morphologies with long, distinct processes and lamellipodia-like structures at their tips.


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 morphology depends on substrate stiffness. (A–D) Representative fluorescence images of microglial cells on substrates of different stiffness. F-actin appears in green, nuclei in blue. (A) On substrates of G′ ~ 100 Pa, microglial cells showed many filopodia-like processes (red arrows). (B) On stiffer substrates (G′ ~ 300 Pa), they showed amoeboid morphologies (red arrow) with significantly fewer processes (p < 0.05, Mann-Whitney U-test). (C,D) On 1000 Pa substrates and on glass, microglial cells had complex morphologies with lamellipodia-like structures at the tips of long processes (red arrows). Scale bar: 10 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Microglia morphology depends on substrate stiffness. (A–D) Representative fluorescence images of microglial cells on substrates of different stiffness. F-actin appears in green, nuclei in blue. (A) On substrates of G′ ~ 100 Pa, microglial cells showed many filopodia-like processes (red arrows). (B) On stiffer substrates (G′ ~ 300 Pa), they showed amoeboid morphologies (red arrow) with significantly fewer processes (p < 0.05, Mann-Whitney U-test). (C,D) On 1000 Pa substrates and on glass, microglial cells had complex morphologies with lamellipodia-like structures at the tips of long processes (red arrows). Scale bar: 10 μm.
Mentions: After 12 h in vitro, microglia cultured on 100 Pa substrates showed many actin-rich filopodia-like processes (44 ± 3, average ± SEM, n = 14) (Figure 2A). Microglial cells on substrates of G′~300 Pa appeared in a more round or amoeboid shape (Figure 2B), with fewer processes than on softer substrates (24 ± 6, n = 5; p < 0.05, Mann-Whitney U-test). Furthermore, F-actin was distributed more homogeneously throughout the cells. The shape of microglia changed drastically when cultured on 1 kPa substrates or on glass (Figures 2C,D). Cells possessed more complex morphologies with long, distinct processes and lamellipodia-like structures at their tips.

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