Abstract
Cell neighbor exchanges are integral to tissue rearrangements in biology, including development and repair. Often these processes occur via topological T1 transitions analogous to those observed in foams, grains and colloids. However, in contrast to in non-living materials the T1 transitions in biological tissues are rate-limited and cannot occur instantaneously due to the finite time required to remodel complex structures at cell-cell junctions. Here we study how this rate-limiting process affects the mechanics and collective behavior of cells in a tissue by introducing this important biological constraint in a theoretical vertex-based model as an intrinsic single-cell property. We report in the absence of this time constraint, the tissue undergoes a motility-driven glass transition characterized by a sharp increase in the intermittency of cell-cell rearrangements. Remarkably, this glass transition disappears as T1 transitions are temporally limited. As a unique consequence of limited rearrangements, we also find that the tissue develops spaitally correlated streams of fast and slow cells, in which the fast cells organize into stream-like patterns with leader-follower interactions, and maintain optimally stable cell-cell contacts. The predictions of this work is compared with existing in-vivo experiments in Drosophila pupal development.
Highlights
Cell neighbor exchange is fundamental to a host of active biological processes, from embryonic development [1,2] to tissue repair [3,4]
To model the collective dynamics of confluent epithelial cells, we introduce an inherent timescale for cells to undergo rearrangements based on the important observation that T1 events in real tissues do not occur instantaneously
When τT1 is short compared to other timescales in the model, we recover a glass transition, occurring way below the motilities large enough to overcome the energetic barriers that cause a cell to become caged
Summary
Cell neighbor exchange is fundamental to a host of active biological processes, from embryonic development [1,2] to tissue repair [3,4]. Curran et al [16] measure T1 rates in Drosophila pupal notum, where a monotonic drop in T1 rate is observed during tissue maturation All these results confirm that is there a natural time delay associated with T1 events, this delay can vary during the developmental process or be modified by mutation. The focus of this work is to study the interplay of active cell motility and the controlled rate of T1 events regulated at the level of individual cells We explore this relation and its consequences within a theoretical approach by a singlecell temporal control on cellular neighbor exchanges in terms of a characteristic timescale for which T1 transitions are stalled. We demonstrate that single-cell control yields realistic neighbor exchange rates and correctly captures the relationship observed between the rate of neighbor exchanges and cellular junctional tensions in a developing Drosophila pupa [16]
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