Abstract
Cells comprising a tissue migrate as part of a collective. In order to coordinate collective multi- cellular migration, each constituent cell integrates local information including chemical signals and mechanical stresses. The boundary between a constituent cell and its immediate neighbors comprises cell-cell junctions and cryptic lamellipodia, but the state of local mechanical stress exerted at that boundary has not been accessible experimentally. As such it is not clear how collective mechanical processes could be coordinated over length scales spanning large multi-cellular assemblies. We report here maps of the stresses exerted within and between cells comprising a monolayer. Within the cell sheet there arise unanticipated fluctuations of mechanical stress that are severe, emerge spontaneously, and ripple across the monolayer. These fluctuations define a rugged stress landscape that becomes increasingly heterogeneous, sluggish, and cooperative with increasing system density. Within that persistently rugged stress landscape, local cellular migrations are found to migrate along local orientations of maximal principal stress. Migrations of both endothelial and epithelial monolayers conform to this behavior, as do breast cancer cell lines before but not after the epithelial-mesenchymal transition. In these diverse cell types, our data indicate that collective migration is governed by a simple but unifying physiological principle: neighboring cells join forces to transmit appreciable intercellular normal stress across local cell-cell junctions, but migrate along orientations of minimal intercellular shear stress.
Highlights
Cells comprising a tissue migrate as part of a collective
At each point within the sheet the local coordinate system (Fig. 1c) can be rotated in the cell plane to find those special orientations along which the local normal stress is maximal and minimal, respectively, defining the two principal stress components and the two corresponding, mutually perpendicular, principal orientations (Fig. 1d; Supplementary Information S1)
Σxx σxy σyx σyy σxy x σxx σmax x σmin severely heterogeneous; normal stresses are mostly positive with values exceeding 300 Pa in regions spanning tens of cells. These regions of predominantly tensile stresses alternate with regions of weakly negative stresses (Fig. 2c). These fluctuations occur steadily over distances spanning multiple cell widths and define a stress landscape that is rugged (Fig. 2c,i), by which we mean that the spatial fluctuations over these relatively short distances are comparable in magnitude to the spatial mean values
Summary
We report high-resolution maps of these stress components everywhere within an advancing monolayer sheet, which serves as a simple experimental model system These stress maps reveal that the local cellular trajectory follows local stress fields that are severely heterogeneous and dramatically cooperative over distances spanning many cell bodies. Appreciable portions of the stress field are approximately isotropic, and the local orientation of cell motion would not be expected to correlate with a stress field possessing no preferred orientation As such, these observations lead naturally to the following prediction: regions of higher stress anisotropy will exhibit stronger alignment between the direction of local maximal principal stress and that of local cellular migration velocity. We constructed the cumulative probability distribution function, P (φ), reasoning that if there were perfect alignment between the orientation of local cellular migration velocity and that of local maximal principal stress, all angles φ would be 0◦ and the cumulative probability distribution would be a step function from
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
