Pedersen John A, Boschetti Federica, Swartz Melody A
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
J Biomech. 2007;40(7):1484-92. doi: 10.1016/j.jbiomech.2006.06.023. Epub 2006 Sep 20.
Interstitial fluid flow has been shown to affect the organization and behavior of cells in 3D environments in vivo and in vitro, yet the forces driving such responses are not clear. Due to the complex architecture of the extracellular matrix (ECM) and the difficulty of measuring fluid flow near cells embedded in it, the levels of shear stress experienced by cells in this environment are typically estimated using bulk-averaged matrix parameters such as hydraulic permeability. While this is useful for estimating average stresses, it cannot yield insight into how local matrix fiber architecture-which is cell-controlled in the immediate pericellular environment-affects the local stresses imposed on the cell surface. To address this, we used computational fluid dynamics to study flow through an idealized mesh constructed of a cubic lattice of fibers simulating a typical in vitro collagen gel. We found that, in such high porosity matrices, the fibers strongly affect the flow fields near the cell, with peak shear stresses up to five times higher than those predicted by the Brinkman equation. We also found that minor remodeling of the fibers near the cell surface had major effects on the shear stress profile on the cell. These findings demonstrate the importance of fiber architecture to the fluid forces on a cell embedded in a 3D matrix, and also show how small modifications in the local ECM can lead to large changes in the mechanical environment of the cell.
间质液流动已被证明会影响体内和体外三维环境中细胞的组织和行为，但驱动这种反应的力尚不清楚。由于细胞外基质（ECM）结构复杂，且难以测量嵌入其中的细胞附近的液流，因此通常使用诸如水力渗透率等体积平均基质参数来估计这种环境中细胞所经历的剪切应力水平。虽然这对于估计平均应力很有用，但它无法深入了解局部基质纤维结构（在紧邻细胞的环境中由细胞控制）如何影响施加在细胞表面的局部应力。为了解决这个问题，我们使用计算流体动力学来研究通过由模拟典型体外胶原凝胶的纤维立方晶格构成的理想化网格的流动。我们发现，在这种高孔隙率基质中，纤维强烈影响细胞附近的流场，峰值剪切应力比布林克曼方程预测的高出五倍。我们还发现，细胞表面附近纤维的微小重塑对细胞上的剪切应力分布有重大影响。这些发现证明了纤维结构对嵌入三维基质中的细胞所受流体力的重要性，也表明了局部细胞外基质的微小改变如何导致细胞力学环境的巨大变化。
