Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Ann Biomed Eng. 2011 Jul;39(7):1849-56. doi: 10.1007/s10439-011-0310-9. Epub 2011 Apr 14.
The mechanism by which cells organize into tissues is fundamental to developmental biology and tissue engineering. Likewise, the disruption of cellular order within tissues is a hallmark of many diseases including cancer and atherosclerosis. Tissue formation is regulated, in part, by a balance between cell-cell cohesion and cell-extracellular matrix (ECM) adhesion. Here, experiments and approaches to alter this balance are discussed, and the nature of this balance in the formation of microvasculature is explored. Using matrices of tailored stiffness and matrix presentation, the role of the mechanical properties and ligand density in angiogenesis has been investigated. Decreasing cell-matrix adhesion by either reducing matrix stiffness or matrix ligand density induces the self-assembly of endothelial cells into network-like structures. These structures are stabilized by the polymerization of the extracellular matrix protein fibronectin. When fibronectin polymerization is inhibited, network formation does not occur. Interestingly, this interplay between substrate mechanics, ECM assembly, and tissue self-assembly is not limited to endothelial cells and has been observed in other cell types as well. These results suggest novel approaches to foster stable cell-cell adhesion and engineer tissues.
细胞组织成组织的机制是发育生物学和组织工程学的基础。同样，组织内细胞秩序的破坏是许多疾病的标志，包括癌症和动脉粥样硬化。组织形成部分受到细胞-细胞黏附和细胞-细胞外基质 (ECM) 黏附之间平衡的调节。本文讨论了改变这种平衡的实验和方法，并探讨了这种平衡在微血管形成中的性质。通过改变基质的硬度和基质的呈现方式，研究了机械特性和配体密度在血管生成中的作用。通过降低基质硬度或基质配体密度减少细胞-基质黏附，诱导内皮细胞自组装成网络状结构。这些结构通过细胞外基质蛋白纤维连接蛋白的聚合来稳定。当纤维连接蛋白聚合被抑制时，网络形成不会发生。有趣的是，这种基质力学、ECM 组装和组织自组装之间的相互作用不仅限于内皮细胞，在其他细胞类型中也观察到了这种相互作用。这些结果为促进稳定的细胞-细胞黏附和工程组织提供了新的方法。
