Zhou Jie, Du Xuewen, Chen Xiaoyi, Xu Bing
Department of Chemistry , Brandeis University , 415 South Street , Waltham , Massachusetts 02453 , United States.
Biochemistry. 2018 Aug 14;57(32):4867-4879. doi: 10.1021/acs.biochem.8b00125. Epub 2018 Jul 25.
Despite the well-established biophysical principle of adhesion-guided in vitro morphogenesis, there are few single synthetic molecular species that can rapidly enable morphogenesis (e.g., a cell monolayer to cell spheroids) in a cell culture because adhesion inherently involves many signals. Here we show the use of adaptive multifunctional supramolecular assemblies of glycopeptides, consisting of cell adhesion sequence and saccharide, to induce cell spheroids rapidly from a monolayer of cells. Having a general architecture of N-terminal capping, glycosylation, and an integrin-binding sequence, the glycopeptides self-assemble to form a dynamic continuum of nanostructures (i.e., from nanoparticles to nanofibers) to affect the interactions of integrins, E-selectin, and cadherins with their natural ligands and to act adaptively according to the cellular environment. Such adaptive (i.e., context-dependent) interactions weaken cell-substratum adhesion and enhance intercellular interactions, which rapidly and transiently induce cell spheroids. This work illustrates the use of supramolecular assemblies of simple glycopeptides to modulate biophysical conditions for regulating cell functions, which is a new approach for developing biomaterials.
尽管粘附引导的体外形态发生这一生物物理原理已得到充分确立，但在细胞培养中，能够快速实现形态发生（例如从细胞单层形成细胞球体）的单一合成分子种类却很少，因为粘附本质上涉及许多信号。在此，我们展示了由细胞粘附序列和糖类组成的糖肽适应性多功能超分子组装体的应用，该组装体能够快速从单层细胞诱导形成细胞球体。糖肽具有N端封端、糖基化和整合素结合序列的一般结构，可自组装形成纳米结构的动态连续体（即从纳米颗粒到纳米纤维），以影响整合素、E-选择素和钙黏蛋白与其天然配体的相互作用，并根据细胞环境进行适应性作用。这种适应性（即依赖于环境的）相互作用会削弱细胞与基质的粘附并增强细胞间相互作用，从而快速且短暂地诱导形成细胞球体。这项工作展示了利用简单糖肽的超分子组装体来调节生物物理条件以调控细胞功能，这是开发生物材料的一种新方法。
