Baker Erin L, Bonnecaze Roger T, Zaman Muhammad H
Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Biophys J. 2009 Aug 19;97(4):1013-21. doi: 10.1016/j.bpj.2009.05.054.
Little is known about the complex interplay between the extracellular mechanical environment and the mechanical properties that characterize the dynamic intracellular environment. To elucidate this relationship in cancer, we probe the intracellular environment using particle-tracking microrheology. In three-dimensional (3D) matrices, intracellular effective creep compliance of prostate cancer cells is shown to increase with increasing extracellular matrix (ECM) stiffness, whereas modulating ECM stiffness does not significantly affect the intracellular mechanical state when cells are attached to two-dimensional (2D) matrices. Switching from 2D to 3D matrices induces an order-of-magnitude shift in intracellular effective creep compliance and apparent elastic modulus. However, for a given matrix stiffness, partial blocking of beta1 integrins mitigates the shift in intracellular mechanical state that is invoked by switching from a 2D to 3D matrix architecture. This finding suggests that the increased cell-matrix engagement inherent to a 3D matrix architecture may contribute to differences observed in viscoelastic properties between cells attached to 2D matrices and cells embedded within 3D matrices. In total, our observations show that ECM stiffness and architecture can strongly influence the intracellular mechanical state of cancer cells.
关于细胞外机械环境与表征动态细胞内环境的机械特性之间复杂的相互作用，我们所知甚少。为了阐明癌症中的这种关系，我们使用粒子追踪微流变学来探究细胞内环境。在三维（3D）基质中，前列腺癌细胞的细胞内有效蠕变柔量显示出随着细胞外基质（ECM）硬度的增加而增加，而当细胞附着于二维（2D）基质时，调节ECM硬度对细胞内机械状态没有显著影响。从2D基质转换到3D基质会导致细胞内有效蠕变柔量和表观弹性模量发生一个数量级的变化。然而，对于给定的基质硬度，β1整合素的部分阻断减轻了由从2D基质结构转换到3D基质结构所引发的细胞内机械状态的变化。这一发现表明，3D基质结构固有的增加的细胞 - 基质相互作用可能导致附着于2D基质的细胞与嵌入3D基质的细胞之间在粘弹性特性上观察到的差异。总的来说，我们的观察结果表明，ECM硬度和结构可以强烈影响癌细胞的细胞内机械状态。
