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Propulsion and navigation within the advancing monolayer sheet.

Kim JH, Serra-Picamal X, Tambe DT, Zhou EH, Park CY, Sadati M, Park JA, Krishnan R, Gweon B, Millet E, Butler JP, Trepat X, Fredberg JJ - Nat Mater (2013)

Bottom Line: Here we show that such a relationship between motion and stress is far from direct.Using monolayer stress microscopy, we probed migration velocities, cellular tractions and intercellular stresses in an epithelial cell sheet advancing towards an island on which cells cannot adhere.We found that cells located near the island exert tractions that pull systematically towards this island regardless of whether the cells approach the island, migrate tangentially along its edge, or paradoxically, recede from it.

View Article: PubMed Central - PubMed

Affiliation: School of Public Health, Harvard University, Boston, Massachusetts 02115, USA.

ABSTRACT
As a wound heals, or a body plan forms, or a tumour invades, observed cellular motions within the advancing cell swarm are thought to stem from yet to be observed physical stresses that act in some direct and causal mechanical fashion. Here we show that such a relationship between motion and stress is far from direct. Using monolayer stress microscopy, we probed migration velocities, cellular tractions and intercellular stresses in an epithelial cell sheet advancing towards an island on which cells cannot adhere. We found that cells located near the island exert tractions that pull systematically towards this island regardless of whether the cells approach the island, migrate tangentially along its edge, or paradoxically, recede from it. This unanticipated cell-patterning motif, which we call kenotaxis, represents the robust and systematic mechanical drive of the cellular collective to fill unfilled space.

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Orientations of tractions, velocities, and principal stresses coincide, diverge, and recoverA–D: Color maps of the ensemble averaged tractions exerted between the monolayer and its substrate (see text for sign convention). A,B,D: x-component of traction, <Tx>, west and east of the island. C: y-component, <Ty>, north of the island (the inset shows <Tx> on the north boundary). These components were selected to reflect the directions roughly normal to the island boundaries. Upstream versus downstream (A,D), <Tx>shows large fluctuations but systematic differences. Regardless of position near a frustrated edge, tractions pull toward that edge. E–H: Color maps showing the systematic buildup of tension and velocity fields (black arrows) at the same locations and times as in panels (A–D). (Due to large gradients of accumulated tensions, the color scale for panels (G) and (H) are expanded for clarity.) I–L: Expanded views of two regions from (F) and one each from (G) and (H). Together with tractions (blue arrows) and the velocity field (black arrows), monolayer stresses are depicted by ellipses, with axes and orientations corresponding to the principal stresses, and iso-tension contours by dashed lines in (I) and (J). Stagnation points are shown by red arrows in (J) and (L). Note the coincidence, divergence and recovery of orientations as the monolayer engulfs the island. Scale bar in panel (A): 100μm. Velocity scale bars in (E) and (J) applies to (F–H) and (I,J,J), respectively.
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Figure 2: Orientations of tractions, velocities, and principal stresses coincide, diverge, and recoverA–D: Color maps of the ensemble averaged tractions exerted between the monolayer and its substrate (see text for sign convention). A,B,D: x-component of traction, <Tx>, west and east of the island. C: y-component, <Ty>, north of the island (the inset shows <Tx> on the north boundary). These components were selected to reflect the directions roughly normal to the island boundaries. Upstream versus downstream (A,D), <Tx>shows large fluctuations but systematic differences. Regardless of position near a frustrated edge, tractions pull toward that edge. E–H: Color maps showing the systematic buildup of tension and velocity fields (black arrows) at the same locations and times as in panels (A–D). (Due to large gradients of accumulated tensions, the color scale for panels (G) and (H) are expanded for clarity.) I–L: Expanded views of two regions from (F) and one each from (G) and (H). Together with tractions (blue arrows) and the velocity field (black arrows), monolayer stresses are depicted by ellipses, with axes and orientations corresponding to the principal stresses, and iso-tension contours by dashed lines in (I) and (J). Stagnation points are shown by red arrows in (J) and (L). Note the coincidence, divergence and recovery of orientations as the monolayer engulfs the island. Scale bar in panel (A): 100μm. Velocity scale bars in (E) and (J) applies to (F–H) and (I,J,J), respectively.

Mentions: Local tractions exerted between the cell and its substrate was measured using Fourier-transform traction microscopy10 (see Methods). At each point the local traction exerted by the cell upon the substrate is necessarily equal and opposite to the traction exerted by the substrate upon the cell (Fig. S2); it is helpful to depict the latter of these here in order that maps of migratory motions versus those of associated tractions would be closely similar if the motions roughly follow substrate-to-cell tractions. Even after averaging across the ensemble, tractions demonstrate strong fluctuations in magnitude and even fluctuations in sign (Fig. 2A–D); such dynamic heterogeneity is also a characteristic feature of collective cellular migration9,10,13. Upstream of the island the x-component of the traction vector,<Tx>, shows a preponderance of blue, indicating that average tractions upstream of the island tend to pull the monolayer eastward – toward the frustrated edge (Fig. 2B). But downstream of the island the x-component of the traction vector shows a preponderance of red, indicating that average tractions downstream of the island tend to pull westward, again toward the frustrated edge (Fig. 2D). Finally, near the north pole, the y-tractions, <Ty>, pull predominantly southward, yet again toward the frustrated edge (Fig. 2C). Importantly, regardless of cellular position along the frustrated edge, cells close to the frustrated edge exert tractions that tend to pull the monolayer toward that edge.


Propulsion and navigation within the advancing monolayer sheet.

Kim JH, Serra-Picamal X, Tambe DT, Zhou EH, Park CY, Sadati M, Park JA, Krishnan R, Gweon B, Millet E, Butler JP, Trepat X, Fredberg JJ - Nat Mater (2013)

Orientations of tractions, velocities, and principal stresses coincide, diverge, and recoverA–D: Color maps of the ensemble averaged tractions exerted between the monolayer and its substrate (see text for sign convention). A,B,D: x-component of traction, <Tx>, west and east of the island. C: y-component, <Ty>, north of the island (the inset shows <Tx> on the north boundary). These components were selected to reflect the directions roughly normal to the island boundaries. Upstream versus downstream (A,D), <Tx>shows large fluctuations but systematic differences. Regardless of position near a frustrated edge, tractions pull toward that edge. E–H: Color maps showing the systematic buildup of tension and velocity fields (black arrows) at the same locations and times as in panels (A–D). (Due to large gradients of accumulated tensions, the color scale for panels (G) and (H) are expanded for clarity.) I–L: Expanded views of two regions from (F) and one each from (G) and (H). Together with tractions (blue arrows) and the velocity field (black arrows), monolayer stresses are depicted by ellipses, with axes and orientations corresponding to the principal stresses, and iso-tension contours by dashed lines in (I) and (J). Stagnation points are shown by red arrows in (J) and (L). Note the coincidence, divergence and recovery of orientations as the monolayer engulfs the island. Scale bar in panel (A): 100μm. Velocity scale bars in (E) and (J) applies to (F–H) and (I,J,J), respectively.
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Related In: Results  -  Collection

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Figure 2: Orientations of tractions, velocities, and principal stresses coincide, diverge, and recoverA–D: Color maps of the ensemble averaged tractions exerted between the monolayer and its substrate (see text for sign convention). A,B,D: x-component of traction, <Tx>, west and east of the island. C: y-component, <Ty>, north of the island (the inset shows <Tx> on the north boundary). These components were selected to reflect the directions roughly normal to the island boundaries. Upstream versus downstream (A,D), <Tx>shows large fluctuations but systematic differences. Regardless of position near a frustrated edge, tractions pull toward that edge. E–H: Color maps showing the systematic buildup of tension and velocity fields (black arrows) at the same locations and times as in panels (A–D). (Due to large gradients of accumulated tensions, the color scale for panels (G) and (H) are expanded for clarity.) I–L: Expanded views of two regions from (F) and one each from (G) and (H). Together with tractions (blue arrows) and the velocity field (black arrows), monolayer stresses are depicted by ellipses, with axes and orientations corresponding to the principal stresses, and iso-tension contours by dashed lines in (I) and (J). Stagnation points are shown by red arrows in (J) and (L). Note the coincidence, divergence and recovery of orientations as the monolayer engulfs the island. Scale bar in panel (A): 100μm. Velocity scale bars in (E) and (J) applies to (F–H) and (I,J,J), respectively.
Mentions: Local tractions exerted between the cell and its substrate was measured using Fourier-transform traction microscopy10 (see Methods). At each point the local traction exerted by the cell upon the substrate is necessarily equal and opposite to the traction exerted by the substrate upon the cell (Fig. S2); it is helpful to depict the latter of these here in order that maps of migratory motions versus those of associated tractions would be closely similar if the motions roughly follow substrate-to-cell tractions. Even after averaging across the ensemble, tractions demonstrate strong fluctuations in magnitude and even fluctuations in sign (Fig. 2A–D); such dynamic heterogeneity is also a characteristic feature of collective cellular migration9,10,13. Upstream of the island the x-component of the traction vector,<Tx>, shows a preponderance of blue, indicating that average tractions upstream of the island tend to pull the monolayer eastward – toward the frustrated edge (Fig. 2B). But downstream of the island the x-component of the traction vector shows a preponderance of red, indicating that average tractions downstream of the island tend to pull westward, again toward the frustrated edge (Fig. 2D). Finally, near the north pole, the y-tractions, <Ty>, pull predominantly southward, yet again toward the frustrated edge (Fig. 2C). Importantly, regardless of cellular position along the frustrated edge, cells close to the frustrated edge exert tractions that tend to pull the monolayer toward that edge.

Bottom Line: Here we show that such a relationship between motion and stress is far from direct.Using monolayer stress microscopy, we probed migration velocities, cellular tractions and intercellular stresses in an epithelial cell sheet advancing towards an island on which cells cannot adhere.We found that cells located near the island exert tractions that pull systematically towards this island regardless of whether the cells approach the island, migrate tangentially along its edge, or paradoxically, recede from it.

View Article: PubMed Central - PubMed

Affiliation: School of Public Health, Harvard University, Boston, Massachusetts 02115, USA.

ABSTRACT
As a wound heals, or a body plan forms, or a tumour invades, observed cellular motions within the advancing cell swarm are thought to stem from yet to be observed physical stresses that act in some direct and causal mechanical fashion. Here we show that such a relationship between motion and stress is far from direct. Using monolayer stress microscopy, we probed migration velocities, cellular tractions and intercellular stresses in an epithelial cell sheet advancing towards an island on which cells cannot adhere. We found that cells located near the island exert tractions that pull systematically towards this island regardless of whether the cells approach the island, migrate tangentially along its edge, or paradoxically, recede from it. This unanticipated cell-patterning motif, which we call kenotaxis, represents the robust and systematic mechanical drive of the cellular collective to fill unfilled space.

Show MeSH
Related in: MedlinePlus