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Cell Mechanics, Structure, and Function Are Regulated by the Stiffness of the Three-Dimensional Microenvironment

Lookup NU author(s): Dr Jinju Chen

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Abstract

This study adopts a combined computational and experimental approach to determine the mechanical, structural, and metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series of linear elastic and hyperelastic finite-element models demonstrated that chondrocytes cultured for 24 h in gels for which the relaxation modulus is <5 kPa exhibit a cellular Youngs modulus of 5 kPa. This is notably greater than that reported for isolated chondrocytes in suspension. The increase in cell modulus occurs over a 24-h period and is associated with an increase in the organization of the cortical actin cytoskeleton, which is known to regulate cell mechanics. However, there was a reduction in chromatin condensation, suggesting that changes in the nucleus mechanics may not be involved. Comparison of cells in 1% and 3% agarose showed that cells in the stiffer gels rapidly develop a higher Youngs modulus of 20 kPa, sixfold greater than that observed in the softer gels. This was associated with higher levels of actin organization and chromatin condensation, but only after 24 h in culture. Further studies revealed that cells in stiffer gels synthesize less extracellular matrix over a 28-day culture period. Hence, this study demonstrates that the properties of the three-dimensional microenvironment regulate the mechanical, structural, and metabolic properties of living cells.


Publication metadata

Author(s): Chen J, Irianto J, Inamdar S, Pravincumar P, Lee DA, Bader DL, Knight MM

Publication type: Article

Publication status: Published

Journal: Biophysical Journal

Year: 2012

Volume: 103

Issue: 6

Pages: 1188-1197

Print publication date: 19/09/2012

Date deposited: 11/01/2013

ISSN (print): 0006-3495

ISSN (electronic): 1542-0086

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.bpj.2012.07.054

DOI: 10.1016/j.bpj.2012.07.054


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