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Cadherin- and Rigidity-Dependent Growth of Lung Cancer Cells in a Partially Confined Microenvironment
T H Hui1,2, Y H Tang1, Z Yan1,2
1Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
ACS Biomaterials Science & Engineering
|January 9, 2021
Summary
Cancer cells adapt to confinement by altering growth direction. Stiff barriers promote cell stacking and increase cadherin expression, impacting proliferation.
Area of Science:
- Cell Biology
- Biophysics
- Cancer Research
Background:
- Tumor cells encounter extracellular barriers during development.
- Understanding cell growth dynamics against confinement is crucial but poorly understood.
Purpose of the Study:
- To investigate the growth dynamics of human lung epithelial carcinoma A549 cells under varying degrees of confinement.
- To identify key factors governing cell growth against physical barriers.
Main Methods:
- Utilized micrometer-sized cylindrical pores with controlled wall stiffness to confine A549 cells.
- Observed cell monolayer growth dynamics and strain levels.
- Developed a model incorporating wall deformability and growth inhibition thresholds.
Main Results:
- Compliant walls allowed monolayers to grow and enlarge pores.
- Stiff walls reduced in-plane growth, increased cell strain, and induced out-of-plane growth (cell stacking).
- Cadherins aggregated at cell junctions, with stiff confinement elevating their expression and N-cadherin inhibition suppressing growth.
Conclusions:
- Cellular response to confinement depends on wall stiffness.
- Cadherins play a significant role in regulating cell proliferation and stress under confinement.
- A biophysical model explains observed growth behaviors based on wall properties and cell stress.
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