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Mapping the dynamics of force transduction at cell-cell junctions of epithelial clusters.

Ng MR, Besser A, Brugge JS, Danuser G - Elife (2014)

Bottom Line: We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters.Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell–cell junctions.Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.

ABSTRACT
Force transduction at cell–cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell–cell junctions. At the multi-cellular scale, cell–cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell–cell adhesions [corrected].

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Force dynamics during cell divisions in cluster shown in Figure 4.(A) Strain energies exerted by individual cells. (B) Fluctuations of cell–cell forces at individual junctions. (C) Total cell–cell forces exerted by individual cells.DOI:http://dx.doi.org/10.7554/eLife.03282.011
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fig4s1: Force dynamics during cell divisions in cluster shown in Figure 4.(A) Strain energies exerted by individual cells. (B) Fluctuations of cell–cell forces at individual junctions. (C) Total cell–cell forces exerted by individual cells.DOI:http://dx.doi.org/10.7554/eLife.03282.011

Mentions: (A–C) A 4-cell cluster undergoing two cell divisions (cell 1 divides into 1 and 5; cell 3 divides into 3 and 6). Top row, fluorescent images of E-cadherin-GFP signals overlaid with traction force field. Vectors originating from the center of each cell reflect the residual traction force of the cell. Bottom row, graphical network representations including residual traction force for each cell and junctional cell–cell forces (see Figure 1). (D–E) Total strain energy on the substrate exerted by the cell cluster and cells 1 and 3 before, during, and after the cell division events. (F–G) Cell–cell force magnitudes exerted by cells 1 and 3 on each of their cell–cell junctions. (H–I) Sum of cell–cell force magnitudes exerted by the whole cluster and cells 1 and 3 before, during, and after the cell division events. See also Figure 4—figure supplement 1 and Video 4.


Mapping the dynamics of force transduction at cell-cell junctions of epithelial clusters.

Ng MR, Besser A, Brugge JS, Danuser G - Elife (2014)

Force dynamics during cell divisions in cluster shown in Figure 4.(A) Strain energies exerted by individual cells. (B) Fluctuations of cell–cell forces at individual junctions. (C) Total cell–cell forces exerted by individual cells.DOI:http://dx.doi.org/10.7554/eLife.03282.011
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300730&req=5

fig4s1: Force dynamics during cell divisions in cluster shown in Figure 4.(A) Strain energies exerted by individual cells. (B) Fluctuations of cell–cell forces at individual junctions. (C) Total cell–cell forces exerted by individual cells.DOI:http://dx.doi.org/10.7554/eLife.03282.011
Mentions: (A–C) A 4-cell cluster undergoing two cell divisions (cell 1 divides into 1 and 5; cell 3 divides into 3 and 6). Top row, fluorescent images of E-cadherin-GFP signals overlaid with traction force field. Vectors originating from the center of each cell reflect the residual traction force of the cell. Bottom row, graphical network representations including residual traction force for each cell and junctional cell–cell forces (see Figure 1). (D–E) Total strain energy on the substrate exerted by the cell cluster and cells 1 and 3 before, during, and after the cell division events. (F–G) Cell–cell force magnitudes exerted by cells 1 and 3 on each of their cell–cell junctions. (H–I) Sum of cell–cell force magnitudes exerted by the whole cluster and cells 1 and 3 before, during, and after the cell division events. See also Figure 4—figure supplement 1 and Video 4.

Bottom Line: We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters.Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell–cell junctions.Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.

ABSTRACT
Force transduction at cell–cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell–cell junctions. At the multi-cellular scale, cell–cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell–cell adhesions [corrected].

Show MeSH
Related in: MedlinePlus