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The elastic moduli of tissues are connected to their states of health and function. The epithelial monolayer is a simple, minimal, tissue model that is often used to gain understanding of mechanical behavior at the cellular or multi-cellular scale. Here we investigate how the elastic modulus of Madin Darby Canine Kidney (MDCK) cells depends on their packing density. Rather than measuring elasticity at the sub-cellular scale with local probes, we characterize the monolayer at the multicellular scale, as one would a thin slab of elastic material. We use a micro-indentation system to apply gentle forces to the apical side of MDCK monolayers, applying a normal force to approximately 100 cells in each experiment. In low-density confluent monolayers, we find that the elastic modulus decreases with increasing cell density. At high densities, the modulus appears to plateau. This finding will help guide our understanding of known collective behaviors in epithelial monolayers and other tissues where variations in cell packing density are correlated with cell motion.
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Microindentation of Fluid‐Filled Cellular Domes Reveals the Contribution of RhoA‐ROCK Signaling to Multicellular Mechanics
Abstract Cellular mechanics encompass both mechanical properties that resist forces applied by the external environment and internally generated forces applied at the location of cell–cell and cell–matrix junctions. Here, the authors demonstrate that microindentation of cellular domes formed by cell monolayers that locally lift off the substrate provides insight into both aspects of cellular mechanics in multicellular structures. Using a modified Hertz contact equation, the force–displacement curves generated by a micro‐tensiometer are used to measure an effective dome stiffness. The results indicate the domes are consistent with the Laplace–Young relationship for elastic membranes, regardless of biochemical modulation of the RhoA‐ROCK signaling axis. In contrast, activating RhoA, and inhibiting ROCK both alter the relaxation dynamics of the domes deformed by the micro‐tensiometer, revealing an approach to interrogate the role of RhoA‐ROCK signaling in multicellular mechanics. A finite element model incorporating a Mooney–Rivlin hyperelastic constitutive equation to describe monolayer mechanics predicts effective stiffness values that are consistent with the micro‐tensiometer measurements, verifying previous measurements of the response of cell monolayers to tension. Overall, these studies establish microindentation of fluid‐filled domes as an avenue to investigate the contribution of cell‐generated forces to the mechanics of multicellular structures.
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- Award ID(s):
- 2034780
- PAR ID:
- 10367699
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Small
- Volume:
- 18
- Issue:
- 21
- ISSN:
- 1613-6810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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