Ushiyama Ai, Ono Mio, Kataoka-Hamai Chiho, Taguchi Tetsushi, Kaizuka Yoshihisa
National Institute for Materials Science, International Center for Materials Nanoarchitectonics , 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan.
Langmuir. 2015 Feb 17;31(6):1988-98. doi: 10.1021/la504523c. Epub 2015 Feb 3.
Modulation of cell adhesion by synthetic materials is useful for a wide range of biomedical applications. Here, we characterized cell adhesion mediated by a semisynthetic molecule, cholesteryl-modified gelatin (chol-gelatin). We found that this hybrid molecule facilitated cell adhesion by connecting two apposed membranes via multiple cholesterol moieties on the gelatin molecules, whereas unmodified gelatin did not bind to cell membranes. Analyses revealed that the rate of the formation of cell adhesions was increased by displaying more cholesterol moieties on the cell membrane. In contrast, the area of the cell adhesion site was unchanged by increasing the number of cholesterol molecules, suggesting that chol-gelatin may suppress cell spreading. Such restriction was not observed in cell adhesion mediated by the mutant of physiological adhesion protein CD2, which lacked its cytoplasmic domain and was unable to connect to cytoplasmic actin filaments, but had a similar affinity for its ligand compared with the chol-gelatin-cell membrane interaction. Further analysis suggested the restriction of cell spreading by chol-gelatin was largely independent of the modulation of the surface force, and thus we hypothesize that the restriction could be in part due to the modulation of cell membrane mechanics by membrane-incorporated chol-gelatin. Our study dissected the two roles of the hybrid molecule in cell adhesion, namely the formation of a molecular connection and the restriction of spreading, and may be useful for designing other novel synthetic agents to modulate various types of cell adhesions.
合成材料对细胞黏附的调节在广泛的生物医学应用中很有用。在此，我们对由半合成分子胆固醇修饰明胶（chol - 明胶）介导的细胞黏附进行了表征。我们发现这种杂合分子通过明胶分子上的多个胆固醇部分连接两个相对的膜来促进细胞黏附，而未修饰的明胶不与细胞膜结合。分析表明，通过在细胞膜上展示更多的胆固醇部分，细胞黏附形成的速率增加。相比之下，增加胆固醇分子的数量对细胞黏附位点的面积没有影响，这表明chol - 明胶可能会抑制细胞铺展。在由生理黏附蛋白CD2的突变体介导的细胞黏附中未观察到这种限制，该突变体缺乏其细胞质结构域，无法连接到细胞质肌动蛋白丝，但与chol - 明胶 - 细胞膜相互作用相比，对其配体具有相似的亲和力。进一步的分析表明，chol - 明胶对细胞铺展的限制在很大程度上与表面力的调节无关，因此我们推测这种限制可能部分归因于膜结合的chol - 明胶对细胞膜力学的调节。我们的研究剖析了这种杂合分子在细胞黏附中的两个作用，即分子连接的形成和铺展的限制，这可能有助于设计其他新型合成剂来调节各种类型的细胞黏附。
