Kasten Annika, Naser Tamara, Brüllhoff Kristina, Fiedler Jörg, Müller Petra, Möller Martin, Rychly Joachim, Groll Jürgen, Brenner Rolf E
Laboratory of Cell Biology, Rostock University Medical Center, Rostock, Germany.
Division for Biochemistry of Joint and Connective Tissue Diseases of the Orthopedic Department, University of Ulm, Ulm, Germany.
PLoS One. 2014 Oct 15;9(10):e109411. doi: 10.1371/journal.pone.0109411. eCollection 2014.
Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
使用合适的细胞黏附配体设计植入物表面以刺激干细胞的特定生物学反应，将推动再生植入物的应用。例如，促进干细胞快速定向迁移的材料将促进组织再生。当接种到均匀固定于NCO-sP(EO-stat-PO)上的纤连蛋白（FN）上时，人骨髓间充质干细胞（MSC）在纤连蛋白上的迁移速度更快、铺展增加，且与在玻璃表面相比，不同细胞成分在纤连蛋白上的黏附组织化更快，而NCO-sP(EO-stat-PO)原本会阻止蛋白质结合和细胞黏附。为了进一步探究FN的结构组织如何控制MSC的行为，生成了宽度在10 µm至80 µm之间且间距在5 µm至20 µm之间、不允许细胞黏附的不同宽度的FN黏附线。根据线宽和间隙的不同，细胞形成相邻的细胞接触、单独排列成线或跨越这些线。随着FN线尺寸的减小，细胞迁移的速度和方向性增加，这与肌动蛋白细胞骨架的组织、细胞核的大小和形状以及黏着斑相关。总之，确定的FN线和间隙能够对细胞成分的结构组织和迁移进行微调。微结构化黏附底物可以模拟体内的细胞外基质，并刺激在组织再生中起作用的细胞机制。
