| Popis: |
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’s 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. Significance statement Cell-cell tensions play an important role in the dynamics of tissue morphogenesis. Mathematical modeling tools have helped understand the role of cell-substrate and cell-cell adhesion in tissue organization. In particular, recent modeling studies have shown that an inferential approach without a constitutive equation can estimate distribution of tensions in a single image of a cell monolayer (CellFIT). Here, we include the dynamics of monolayer morphogenesis in the estimation of cell-cell tensions. Such a formulation, termed DLITE, performs better across time in both synthetic geometries and time series of hIPS cell colonies with endogenously expressed GFP-tagged-ZO-1. We also show that DLITE is robust to digitization ambiguities during segmentation. Such a method can shed some light on physical mechanisms that drive morphogenesis. |
