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DLITE uses cell-cell interface movement to better infer cell-cell tensions

By R. Vasan, M.M. Maleckar, C.D. Williams, P. Rangamani

Posted 05 Feb 2019
bioRxiv DOI: 10.1101/541144 (published DOI: 10.1016/j.bpj.2019.09.034)

Cell shapes and connectivities evolve over time as colony shapes change or embryos develop. Shapes of intercellular interfaces are closely coupled with the forces resulting from actomyosin interactions, membrane tension, or cell-cell adhesion. While it is possible to computationally infer cell-cell forces from a mechanical model of collective cell behavior, doing so for temporally evolving forces in a manner that is robust to digitization difficulties is challenging. Here, we introduce a method for Dynamic Local Intercellular Tension Estimation (DLITE) that infers such temporal force evolutions with less sensitivity to digitization ambiguities or errors. This method builds upon prior work on single time points (CellFIT). We validate our method using synthetic geometries. DLITE inferred cell colony tension evolutions correlate better with ground truth for these synthetic geometries than tension values inferred from methods that consider each time point in isolation. We introduce cell connectivity errors, angle estimate errors, connection mislocalization, and connection topological changes to synthetic data and show that DLITE has reduced sensitivity to these conditions. Finally, we apply DLITE to time series of human induced pluripotent stem (hIPS) cell colonies with endogenously expressed GFP-tagged ZO-1. We find major topological changes in cell connectivity, e.g. mitosis, can result in an increase in tension. This supports a correlation between the dynamics of cell-cell forces and colony rearrangement.

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