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In tissue formation and repair, the epithelium undergoes complex patterns of motion driven by the active forces produced by each cell. Although the principles governing how the forces evolve in time are not yet clear, it is often assumed that the contractile stresses within the cell layer align with the axis defined by the body of each cell. Here, we simultaneously measured the orientations of the cell shape and the cell-generated contractile stresses, observing correlated, dynamic domains in which the stresses were systematically misaligned with the cell body. We developed a continuum model that decouples the orientations of contractile stress and cell body. The model recovered the spatial and temporal dynamics of the regions of misalignment in the experiments. These findings reveal that the cell controls its contractile forces independently from its shape, suggesting that the physical rules relating cell forces and cell shape are more flexible than previously thought.
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Continuum theory for confluent cell monolayers: Interplay between cell growth, division, and intercalation
Mechanical forces generated by dynamic cellular activities play a crucial role in the morphogenesis and growth of biological tissues. While the influence of mechanics is clear, many questions arise regarding the way by which mechanical forces communicate with biological processes at the level of a confluent cell population. Some answers may be found in the development of mathematical models that are capable of describing the emerging behavior of a large population of active agents based on individualistic rules (single-cell response). In this perspective, the present work presents a continuum-scale model that can capture, in an average sense, the active mechanics and evolution of a confluent tissue with or without external mechanical constraints. For this, we conceptualize a confluent cell population (in a monolayer) as a deformable dynamic network, where a single cell can modify the topology of its neighborhood by swapping neighbors or dividing. With this description, we use concepts from statistical mechanics and the transient network theory to derive an equivalent active visco-elastic continuum model, which can recapitulate some of the salient features of the underlying network at the macroscale. Without loss of generality, the cell network is here assumed to follow well-known rules used in vertex model simulations, which are: (a) cell elasticity based on its bulk and cortical elasticity, (b) cell intercalation (or T1 transition), and (c) cell proliferation (expansion and division). We show, through examples and illustrations, that the model is able to characterize complex cross-talk between mechanical forces and biological processes, which are likely to drive the emergent growth and deformation of cell aggregates.
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- Award ID(s):
- 2135057
- PAR ID:
- 10477410
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Journal of the Mechanics and Physics of Solids
- Volume:
- 181
- ISSN:
- 0022-5096
- Page Range / eLocation ID:
- 105443
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1016/j.jmps.2023.105443
