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Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment

Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment
Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment
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 Young’s 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 Young’s 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
0006-3495
1188-1197
Chen, J.
116323ca-c4fd-4be2-96cb-a54d6cec5cc4
Irianto, J.
771f6f0d-ad0b-446c-be14-46c238744812
Inamdar, S.
454d9194-48cd-4f61-a5a2-04e010d6dabc
Pravincumar, P.
6b64d04a-9921-478e-ac22-0d1baf89e4c7
Lee, D.A.
fbbf7169-d08b-4deb-ae87-a2cbd97c58e7
Bader, Dan L.
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Knight, M.M.
eaff1c5c-595c-4b27-bb12-654dcfa0c1cb
Chen, J.
116323ca-c4fd-4be2-96cb-a54d6cec5cc4
Irianto, J.
771f6f0d-ad0b-446c-be14-46c238744812
Inamdar, S.
454d9194-48cd-4f61-a5a2-04e010d6dabc
Pravincumar, P.
6b64d04a-9921-478e-ac22-0d1baf89e4c7
Lee, D.A.
fbbf7169-d08b-4deb-ae87-a2cbd97c58e7
Bader, Dan L.
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Knight, M.M.
eaff1c5c-595c-4b27-bb12-654dcfa0c1cb

Chen, J., Irianto, J., Inamdar, S., Pravincumar, P., Lee, D.A., Bader, Dan L. and Knight, M.M. (2012) Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment. Biophysical Journal, 103 (6), 1188-1197. (doi:10.1016/j.bpj.2012.07.054). (PMID:22995491)

Record type: Article

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 Young’s 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 Young’s 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

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Published date: 19 September 2012
Organisations: Faculty of Health Sciences

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Local EPrints ID: 347080
URI: http://eprints.soton.ac.uk/id/eprint/347080
ISSN: 0006-3495
PURE UUID: 76fb7bcd-5e95-4989-9392-fa73be8a6ce1
ORCID for Dan L. Bader: ORCID iD orcid.org/0000-0002-1208-3507

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Date deposited: 17 Jan 2013 12:03
Last modified: 14 Mar 2024 12:45

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Contributors

Author: J. Chen
Author: J. Irianto
Author: S. Inamdar
Author: P. Pravincumar
Author: D.A. Lee
Author: Dan L. Bader ORCID iD
Author: M.M. Knight

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