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During embryonic morphogenesis, tissues undergo dramatic deformations in order to form functional organs. Similarly, in adult animals, living cells and tissues are continually subjected to forces and deformations. Therefore, the success of embryonic development and the proper maintenance of physiological functions rely on the ability of cells to withstand mechanical stresses as well as their ability to flow in a collective manner. During these events, mechanical perturbations can originate from active processes at the single-cell level, competing with external stresses exerted by surrounding tissues and organs. However, the study of tissue mechanics has been somewhat limited to either the response to external forces or to intrinsic ones. In this work, we use an active vertex model of a 2D confluent tissue to study the interplay of external deformations that are applied globally to a tissue with internal active stresses that arise locally at the cellular level due to cell motility. We elucidate, in particular, the way in which this interplay between globally external and locally internal active driving determines the emergent mechanical properties of the tissue as a whole. For a tissue in the vicinity of a solid-fluid jamming or unjamming transition, we uncover a host of fascinating rheological phenomena, including yielding, shear thinning, continuous shear thickening, and discontinuous shear thickening. These model predictions provide a framework for understanding the recently observed nonlinear rheological behaviors in vivo.
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A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics
Many critical biological processes, like wound healing, require densely packed cell monolayers/tissues to transition from a jammed solid-like to a fluid-like state. Although numerical studies anticipate changes in the cell shape alone can lead to unjamming, experimental support for this prediction is not definitive because, in living systems, fluidization due to density changes cannot be ruled out. Additionally, a cell’s ability to modulate its motility only compounds difficulties since even in assemblies of rigid active particles, changing the nature of self-propulsion has non-trivial effects on the dynamics. Here, we design and assemble a monolayer of synthetic cell-mimics and examine their collective behaviour. By systematically increasing the persistence time of self-propulsion, we discovered a cell shape-driven, density-independent, re-entrant jamming transition. Notably, we observed cell shape and shape variability were mutually constrained in the confluent limit and followed the same universal scaling as that observed in confluent epithelia. Dynamical heterogeneities, however, did not conform to this scaling, with the fast cells showing suppressed shape variability, which our simulations revealed is due to a transient confinement effect of these cells by their slower neighbors. Our experiments unequivocally establish a morphodynamic link, demonstrating that geometric constraints alone can dictate epithelial jamming/unjamming.
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- Award ID(s):
- 2046683
- PAR ID:
- 10586154
- Publisher / Repository:
- Springer Nature
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 15
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41467-024-49044-z
