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Published on: June 2, 2023
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Cell cycle-dependent active stress drives epithelia remodeling.
John Devany1, Daniel M Sussman2,3, Takaki Yamamoto4
1Department of Physics, Institute for Biophysical Dynamics, James Franck Institute, University of Chicago, Chicago, IL 60637.
Summary
Epithelial cell shape and dynamics are regulated by cell cycle progression and mechanical forces. This study reveals how cell shape changes influence tissue remodeling and homeostasis, linking cell mechanics to tissue architecture.
Area of Science:
- Cell Biology
- Biophysics
- Tissue Engineering
Background:
- Epithelial tissues maintain complex architectures crucial for function, adapting to development, wounding, and homeostasis.
- Cell shape is a key regulator of epithelial tissue function, influencing differentiation, proliferation, and motility.
- Understanding the dynamic remodeling of epithelial monolayers is essential for tissue repair and disease modeling.
Purpose of the Study:
- To investigate the relationship between cell shape changes and epithelial monolayer remodeling.
- To identify order parameters controlling epithelial architecture using the active vertex model.
- To elucidate the role of cell cycle dynamics and mechanical forces in establishing tissue architecture.
Main Methods:
- Studied epithelial monolayer remodeling under varying extracellular matrix stiffness and pharmacological perturbations.
- Quantified cell shape, dynamics, and proliferation rates.
- Utilized the active vertex model to analyze tissue remodeling and identify order parameters.
- Investigated cell cycle variation in junctional tension as a source of active stress.
Main Results:
- Monolayer remodeling leads to arrested motion and more regular cell shapes, a robust process across perturbations.
- Extracellular matrix stiffness affects cell density at motion arrest, but not final cell shape.
- Pharmacological perturbations alter cell shape at dynamics arrest, indicating varied active stress.
- Final cell shape strongly correlates with cell proliferation rate; cell cycle inhibition halts motility.
- Cell cycle variations in junctional tension contribute to active stress in epithelial monolayers.
Conclusions:
- Epithelial tissue architecture arises from the interplay between cell mechanics and cell cycle-driven stresses.
- Cell shape dynamics are critical for tissue homeostasis and remodeling.
- The active vertex model provides insights into the order parameters governing epithelial architecture.
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