Wang Yiqun, Yao Yuan
School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China.
Langmuir. 2020 Mar 3;36(8):2129-2135. doi: 10.1021/acs.langmuir.9b03314. Epub 2020 Feb 18.
In natural tissue, nanofibrils in extracellular matrix (ECM), such as collagen fibrils, direct cell migration through contacting guidance. The contacting nanofibers on cell-ECM interface are reorganized from curl fibers to straightened fibers. However, how these nanofibers regulate single cell migration remains obscure. To investigate this issue, we fabricated collagen/polymer based biomimetic nanofiber sheets of varying topography. And we selected tumorigenic cell KGN and nontumorigenic cell 293T for comparison. We found KGN showed higher sensitivity to the nanofiber alignment rather than the nontumorigenic cell 293T, in morphological change, trajectory adaptation, and velocity variation. We also found aligned nanofibers shaped both KGN and 293T into elongated spindle morphology. Comparatively, KGN had greater perimeter and lower roundness than 293T. To study the dynamics of single cell migration of KGN and 293T, we conducted trajectory tracking and siRNA validation on regulatory proteins. We found nanofibers of varying topography regulated the patterns of single cell migration differently. For KGN cell, β-catenin, Rac1, and Cdc42 participated in its directional migration, but it was impervious to vimentin. Comparatively, epithelial cell 293T involved vimentin in its directional migration.
在天然组织中,细胞外基质(ECM)中的纳米纤维,如胶原纤维,通过接触引导来指导细胞迁移。细胞-ECM界面上的接触纳米纤维从卷曲纤维重新组织为伸直纤维。然而,这些纳米纤维如何调节单细胞迁移仍不清楚。为了研究这个问题,我们制备了具有不同形貌的基于胶原蛋白/聚合物的仿生纳米纤维片。并且我们选择了致瘤细胞KGN和非致瘤细胞293T进行比较。我们发现,在形态变化、轨迹适应和速度变化方面,KGN对纳米纤维排列的敏感性高于非致瘤细胞293T。我们还发现排列的纳米纤维将KGN和293T都塑造成细长的纺锤体形态。相比之下,KGN的周长比293T更大,圆度更低。为了研究KGN和293T单细胞迁移的动力学,我们对调节蛋白进行了轨迹跟踪和siRNA验证。我们发现不同形貌的纳米纤维对单细胞迁移模式的调节方式不同。对于KGN细胞,β-连环蛋白、Rac1和Cdc42参与其定向迁移,但波形蛋白对其无影响。相比之下,上皮细胞293T的定向迁移涉及波形蛋白。