Biphasic response of cell invasion to matrix stiffness in three-dimensional biopolymer networks.
Biphasic response of cell invasion to matrix stiffness in three-dimensional biopolymer networks.
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DOI：
10.1016/j.actbio.2014.11.003
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发表时间：
2015-02
影响因子：
9.7
通讯作者：
Fabry B
中科院分区：
文献类型：
--
作者：
Lang NR;Skodzek K;Hurst S;Mainka A;Steinwachs J;Schneider J;Aifantis KE;Fabry B
当细胞与粘附基质接触时，它们开始扩散并以取决于细胞外基质硬度的速度迁移。在平坦表面上，迁移速度随着基质刚度而降低，主要是由于局部粘连的稳定性增加。在三维（3D）环境中，细胞迁移被认为是由周围基质施加的空间位阻额外受损。然而，对于多孔3D生物聚合物网络如胶原凝胶，基质刚度对细胞迁移的影响难以与基质孔径和粘附配体密度的影响分开，因此是未知的。在这里，我们使用戊二醛作为交联剂，以增加刚度的自组装胶原蛋白生物聚合物网络独立的胶原蛋白浓度或孔径。将乳腺癌细胞接种在三维胶原凝胶表面，培养3天后测量浸润深度。细胞在孔径大于5 μm的凝胶中的侵袭性随凝胶刚度的增加而增加，而在孔径较小的凝胶中的侵袭性随凝胶刚度的增加而降低。这些数据表明，3D细胞侵入通过更高的基质刚度而增强，与2D中的细胞行为相反，只要孔径不低于引起过度空间位阻的临界值。这些发现对于优化软组织植入物的再细胞化或癌症研究中3D侵袭模型的设计可能很重要。
When cells come in contact with an adhesive matrix, they begin to spread and migrate with a speed that depends on the stiffness of the extracellular matrix. On a flat surface, migration speed decreases with matrix stiffness mainly due to an increased stability of focal adhesions. In a 3-dimensional (3D) environment, cell migration is thought to be additionally impaired by the steric hindrance imposed by the surrounding matrix. For porous 3D biopolymer networks such as collagen gels, however, the effect of matrix stiffness on cell migration is difficult to separate from effects of matrix pore size and adhesive ligand density, and is therefore unknown. Here we used glutaraldehyde as a crosslinker to increase the stiffness of self-assembled collagen biopolymer networks independently of collagen concentration or pore size. Breast carcinoma cells were seeded onto the surface of 3D collagen gels, and the invasion depth was measured after 3 days of culture. Cell invasion in gels with pore sizes larger than 5 μm increased with higher gel stiffness, whereas invasion in gels with smaller pores decreased with higher gel stiffness. These data show that 3D cell invasion is enhanced by higher matrix stiffness, opposite to cell behavior in 2D, as long as the pore size does not fall below a critical value where it causes excessive steric hindrance. These findings may be important for optimizing the recellularization of soft tissue implants or for the design of 3D invasion models in cancer research.