Schaumann, EN; Staddon, MF; Gardel, ML; Banerjee, S; (2018) Force localization modes in dynamic epithelial colonies. Molecular Biology of the Cell , 29 (23) pp. 2801-2909. 10.1091/mbc.E18-05-0336.

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Abstract

Collective cell behaviors, including tissue remodeling, morphogenesis and cancer metastasis rely on dynamics between cells, their neighbors and the extracellular matrix. The lack of quantitative models precludes understanding of how cell-cell and cell-matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modelling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an Active Adherent Vertex Model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues. Movie S1 Movie S1 Dynamic traction stresses in a micropatterned colony of motile MDCK cells. (Left) Stargazin-GFP labeled MDCK cells displaying intercalations and movement along with large cell shape changes, while retaining the overall colony shape. (Right) Traction stresses associated with the cells. While traction stresses are present along the colony periphery, they display no preferred orientation with respect to the colony edge. Movie S2 Movie S2 Movie of a vertex model simulation for a solid-like colony. (Left) Cell shapes and focal adhesion locations for cells on a patterned substrate. (Right) Traction heatmaps associated with the cells shown. Traction stresses are localized almost completely to the colony edge, and maintain a steady-state over the course of the simulation. Movie S3 Movie S3 Movie of a vertex model simulation for a fluid-like colony. (Left) Cell shapes and focal adhesion locations for cells on a patterned substrate. (Tight) Traction heatmaps associated with the cells shown. Significant traction stresses along the colony interior accompany cell shape changes. Interior traction stresses are also more dynamic in the fluidized case, with appreciable reorganization over the simulation time. Movie S4 Movie S4 3.5 hour long movie of the colony featured in Figure 5A. (Left) Phase contrast images showing scarce cell shape change and absence of neighbor exchanges over the duration of the experiment. (Right) Traction heatmaps corresponding to the phase contrast images. Traction stress peaks are predominantly localized to the colony periphery, remain relatively static, and tend to point inward and perpendicular to the colony edge. Movie S5 Movie S5 3.5 hour long movie of the colony featured in Figure 5B. (Left) Phase contrast images showing large-scale cell movement, shape changes, and neighbor rearrangements. (Right) Traction heatmaps corresponding to the phase contrast images. Traction stresses are dispersed throughout the colony and hot spots move in conjunction with cellular motions. Movie S6 Movie S6 Movie of the simulated cell division shown in Figure 6C,D. (Left) Simulation images showing a cell, highlighted in red, undergoing a division. (Right) Traction heatmaps corresponding to the simulation images. Traction is initially localized to the colony periphery. As the dividing cell pinches, traction is localized around the cell and is dissipated once the daughter cells relax. Movie S7 Movie S7 Movie of the simulated induced cell rotation shown in Figure 7C,D. (Left) Simulation images showing cells in a circular micropattern undergoing spontaneous rotation due to polarity alignment. (Right) Traction heatmaps corresponding to the simulation images. Traction can localize around cells inside away from the colony periphery, and move with the rotating cells.

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