title: Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment.
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.
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Irianto
authors.forename: S
authors.initials: S
authors.lastname: Inamdar
authors.forename: P
authors.initials: P
authors.lastname: Pravincumar
authors.forename: D A
authors.initials: DA
authors.lastname: Lee
authors.forename: D L
authors.initials: DL
authors.lastname: Bader
authors.forename: M M
authors.initials: MM
authors.lastname: Knight
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D001696:Biomechanical Phenomena; D002467:Cell Nucleus / Q000378:metabolism; D060833:Cellular Microenvironment; D019902:Chondrocytes / Q000166:cytology; D002843:Chromatin / Q000378:metabolism; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism; D020342:Finite Element Analysis; D055595:Mechanical Phenomena
chemical_list: D002843:Chromatin