Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science (CEMS), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
J Am Chem Soc. 2020 Dec 16;142(50):20994-21003. doi: 10.1021/jacs.0c03425. Epub 2020 Dec 3.
The self-assembly of biological molecules is an important pathway to understanding the molecular basis of complex metabolic events. The presence of a cosolvent in an aqueous solution during the self-assembly process can promote the formation of kinetically trapped metastable intermediates. In nature, a category of cosolvents termed osmolytes can work to strengthen the hydrogen-bond network of water such that the native states of certain proteins are favored, thus modulating their function and stability. However, identifying cosolvents that act as osmolytes in biomimetic applications, such as the self-assembly of soft materials, remains challenging. The present work examined the effects of ethanol (EtOH) and acetonitrile (ACN) as cosolvents on the self-assembly of the amphiphilic polypeptide PSar-(l-Leu-Aib) (S30L12), which incorporates α-helical hydrophobic blocks, in aqueous solution. The results provided a direct observation of morphological behavior of S30L12 as a function of solvent composition. Morphological transitions were investigated using transmission electron microscopy, while the packing of peptide molecules was assessed using circular dichroism analyses and evaluations of membrane fluidity. In the EtOH/HO mixtures, the EtOH strengthened the hydrogen-bond network of the water, thus limiting the hydrophobic hydration of S30L12 assemblies and enhancing hydrophobic interactions between assemblies. In contrast, ACN formed self-associated nanoclusters in water and at the hydrophobic cores of peptide assemblies to stabilize the edges exposed to bulk water and enhance the assembly kinetics. Fourier transform infrared (FT-IR) analysis indicated that both EtOH and ACN can modify the self-assembly of biomaterials in the same manner as osmolyte protectants or denaturants.
生物分子的自组装是理解复杂代谢事件的分子基础的重要途径。在自组装过程中，水相溶液中存在共溶剂可以促进动力学捕获的亚稳中间体的形成。在自然界中，一类被称为渗透剂的共溶剂可以增强水的氢键网络，从而有利于某些蛋白质的天然状态，从而调节它们的功能和稳定性。然而，在仿生应用中，如软物质的自组装中，识别作为渗透剂的共溶剂仍然具有挑战性。本工作研究了乙醇（EtOH）和乙腈（ACN）作为共溶剂对两亲性多肽 PSar-(l-Leu-Aib)（S30L12）在水溶液中自组装的影响，该多肽含有α-螺旋疏水性块。结果提供了 S30L12 作为溶剂组成函数的形态行为的直接观察。使用透射电子显微镜研究了形态转变，同时使用圆二色性分析和膜流动性评估评估肽分子的组装。在 EtOH/HO 混合物中，EtOH 增强了水的氢键网络，从而限制了 S30L12 组装体的疏水性水合作用，并增强了组装体之间的疏水性相互作用。相比之下，ACN 在水中形成自缔合的纳米团簇，并在肽组装体的疏水区核心形成，以稳定暴露于本体水的边缘并增强组装动力学。傅里叶变换红外（FT-IR）分析表明，EtOH 和 ACN 都可以以与渗透保护剂或变性剂相同的方式修饰生物材料的自组装。
