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Aashrith Saraswathibhatla

Publications and source records attributed to Aashrith Saraswathibhatla.

3 recordsLinked to original sources

Cell Shape Emerges from Motion

We perform cell segmentation on images from experimental studies of confluent, mobile cells in epithelial monolayers and show that these systems possess a broad, positively-skewed shape parameter distribution $P(\mathcal{A})$, where $\mathcal{A}=p^2/4πa$, $p$ is the perimeter, and $a$ is area of each cell. $P(\mathcal{A})$ is peaked at a value higher than the typical shape parameter $\mathcal{A}^* \sim 1.15$ that occurs for randomly packed, static confluent cell monolayers. The distribution does not arise from a heterogeneous population of cells with different fixed $\mathcal{A}$, nor can it arise from cell shape fluctuations from strains below the elastic limit. Instead, we find that all cells in each monolayer sample $\mathcal{A}$ values that span the full shape parameter distribution. We develop a deformable particle model that allows cell perimeter to adapt to local forces during cell motion, and this model recovers $P(\mathcal{A})$ to within $5\%$ for both MDCK and HaCaT epithelial cell monolayers. These results emphasize that confluent epithelial monolayers of mobile cells generate a well-defined broad shape parameter distribution that is independent of the initial cell shapes.

cond-mat.soft↗

Coordinated tractions increase the size of a collectively moving pack in a cell monolayer

Cells in an epithelial monolayer coordinate motion with their neighbors giving rise to collectively moving packs of sizes spanning multiple cell diameters. The physical mechanism controlling the pack size, however, remains unclear. A potential mechanism comes from assuming that cell-substrate traction forces persist over some time scale: with large enough persistence time, collective cell packs emerge. To test this hypothesis, we measured the velocity and net traction of each cell. The data showed that in addition to having some temporal persistence, tractions were spatially correlated, suggesting that cells coordinate with their neighbors to apply tractions in the same direction. Chemical inhibitors and activators of actomyosin contraction were used to determine effects of altering the traction persistence and alignment. Numerical simulations based on the self-propelled Voronoi model, augmented to include both traction persistence and alignment and calibrated against the experimental data, matched the experimentally measured pack size. The model identified that if there were no alignment of traction between neighboring cells, the size of the collective pack would be substantially smaller than observed in the experiments. Hence, combining experiments and a simple mechanical model, this study confirms the long-standing assumption of traction persistence and adds the notion of traction alignment between neighbors. Together, persistence and alignment are two factors controlling the size of a collectively moving cell pack.

physics.bio-ph↗

Tractions and stress fibers control cell shape and rearrangements in collective cell migration

Key to collective cell migration is the ability of cells to rearrange their position with respect to their neighbors. Recent theory and experiments demonstrated that cellular rearrangements are facilitated by cell shape, with cells having more elongated shapes and greater perimeters more easily sliding past their neighbors within the cell layer. Though it is thought that cell perimeter is controlled primarily by cortical tension and adhesion at each cell's periphery, experimental testing of this hypothesis has produced conflicting results. Here we studied collective cell migration in an epithelial monolayer by measuring forces, cell perimeters, and motion, and found all three to decrease with either increased cell density or inhibition of cell contraction. In contrast to previous understanding, the data suggest that cell shape and rearrangements are controlled not by cortical tension or adhesion at the cell periphery but rather by the stress fibers that produce tractions at the cell-substrate interface. This finding is confirmed by an experiment showing that increasing tractions reverses the effect of density on cell shape and rearrangements. Our study therefore reduces the focus on the cell periphery by establishing cell-substrate traction as a major physical factor controlling cell shape and motion in collective cell migration.

physics.bio-ph↗