DLITE: Dynamic Local Intercellular Tension Estimation

Abstract

Abstract The shape of cell-cell interfaces and the forces resulting from actomyosin interactions, mem-brane tension, or cell-cell adhesion are closely coupled. For example, the tight junction protein, ZO-1, forms a link between the force-bearing actin cortex and the rest of the tight junction protein (TJP) complex, regulating epithelial cell differentiation and the flux of solutes across epithelia. Here we introduce a method for Dynamic Local Intercellular Tension Estimation (DLITE) to computationally infer the evolution of cell-cell forces from a mechanical model of collective cell behaviour. This builds upon prior work in the field (CellFIT, Brodland et al., PloS one 9.6 (2014): e99116). We validate our estimated forces against those predicted by Surface Evolver simulations. Inferred tensions of a cell colony rearranging over time correlate better with the ground truth for our method (DLITE) than for prior methods intended for single time-points. DLITE is robust to both skeletonization errors and topological changes. Finally, we used DLITE in WTC-11 human induced pluripotent stem (hIPS) cells endogenously expressing ZO-1 GFP to find that major topo-logical changes in cell connectivity, e.g. mitosis, can result in an increase in tension. This suggests a correlation between the dynamics of cell-cell forces and colony rearrangement.