Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, United Kingdom.
Biophys J. 2012 Sep 19;103(6):1188-97. doi: 10.1016/j.bpj.2012.07.054.
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.
本研究采用计算与实验相结合的方法，确定了三维水凝胶中培养的分离软骨细胞的力学、结构和代谢特性。一系列线性弹性和超弹性有限元模型表明，在松弛模量<5 kPa 的凝胶中培养 24 h 的软骨细胞表现出约 5 kPa 的细胞杨氏模量。这明显大于在悬浮液中分离的软骨细胞的报道值。细胞模量的增加发生在 24 小时内，并与皮质肌动蛋白细胞骨架组织的增加有关，已知该组织调节细胞力学。然而，染色质凝聚减少，表明核力学的变化可能不涉及。比较 1%和 3%琼脂糖中的细胞表明，在较硬的凝胶中，细胞迅速发展出更高的杨氏模量约 20 kPa，是在较软的凝胶中观察到的六倍。这与更高水平的肌动蛋白组织和染色质凝聚有关，但仅在培养 24 小时后。进一步的研究表明，在较硬的凝胶中，细胞在 28 天的培养期间合成的细胞外基质较少。因此，本研究表明，三维微环境的特性调节活细胞的力学、结构和代谢特性。
