蛋白质错误折叠形成淀粉样聚集体是许多神经退行性疾病的主要诱因。体内蛋白质的纤维化与分子表面尤其是生物膜表面有重要关联。研究生物膜表面的性质如何影响蛋白质的纤维化对理解神经退行性疾病的发病机理非常重要。手性作为生物膜表面的主要性质，其如何影响蛋白质纤维化目前仍不清楚。我们从仿生的角度出发，采用不同手性的半胱氨酸修饰的氧化石墨烯(R(S)-Cys-GO)作为模型来研究表面的手性对淀粉样肽(Aβ_40)纤维化的影响。

我们通过EDC/NHS缩合的方法，将不同手性的半胱氨酸分子接枝到羧基化的GO上，然后通过原子力显微镜、拉曼、X-射线光电子能谱、X-射线能量色散谱、紫外可见光谱等测试表征手段对修饰后的GO进行表征。

我们采用ThT荧光标记法、原子力显微镜、石英质量微天平等方法研究了不同手性的半胱氨酸修饰的GO与Aβ_40的相互作用。结果表明R-Cys-GO能够抑制Aβ_40在表面的吸附、成核以及随后的增长过程，而S-Cys-GO却会促进这些过程。我们通过圆二色谱等方法测定了不同手性的半胱氨酸修饰的GO对Aβ_40纤维化过程中构象转变的影响。结果表明，表面手性能够显著影响Aβ_40纤维化过程中的α-螺旋构象到β-折叠构象的转变。

为了研究表面手性差异性的起源，我们分别将GO表面的半胱氨酸分子的羧基或者巯基保护起来，研究这些不同手性的半胱氨酸衍生物修饰的GO对Aβ_40纤维化的影响。结果表明，羧基的保护会减弱不同手性的GO衍生物在影响Aβ_40纤维化中的差异性；而巯基被保护后，相应的GO衍生物对Aβ_40纤维化的影响几乎没有差异。这表明这些基团参与了与Aβ_40的相互作用。荧光滴定和核磁共振的结果表明手性分子与多肽之间的立体相互作用可能是这种手性差异性的起源。进一步实验表明，表面的存在能够将手性分子与多肽之间的相互作用的差异性体现出来。GO表面与手性分子之间的距离也会影响这种手性差异性的体现，只有两者之间的距离足够近时，表面才能参与到手性分子和多肽的相互作用中使这种手性差异性体现出来。

这些结果揭示了生物膜表面的手性在蛋白质纤维化中的重要作用，为理解蛋白质的纤维化提供了新的启示。

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