Fiora Maria Mercedes, Xing Huihua, Cathcarth Marilina, Garate Octavio, Herrera Santiago, Picco Agustin S, Ybarra Gabriel, Conda-Sheridan Martin, Tagliazucchi Mario
Instituto Nacional de Tecnología Industrial, Micro y Nanotecnologías San Martín B1650WAB Buenos Aires Argentina.
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Inorgánica Analítica y Química Física Pabellón 2, Ciudad Universitaria, Ciudad Autónoma de Buenos Aires C1428 Argentina
Chem Sci. 2025 Jul 3. doi: 10.1039/d5sc02935j.
The self-assembly of peptide amphiphiles (PAs) in aqueous solution yields nanoconstructs displaying a rich spectrum of sizes and morphologies, including micelles, fibers, and lamellar ribbons. The morphology impacts the bioactivity of the PAs and, thus, efforts have been made to control it by tuning their molecular structure or the solution pH. However, synthesizing new PAs is time consuming and biomedical applications limit the pH to physiologically relevant ranges. This work demonstrates that the composition of a binary mixture of co-assembled PAs serves as a powerful approach to exert rational control over the morphology, size and transition pHs of the supramolecular nanostructures. We combined light scattering, SAXS, TEM and AFM experiments and theoretical predictions using a Molecular Theory (MOLT) to construct composition-pH morphology diagrams for three relevant PA mixtures. For CKK/CKKK mixtures (C: palmitoyl and K: lysine), we demonstrate fine tuning of the micelle-to-fiber transition pH by varying the composition of the system. For a mixture of oppositely charged PAs, CEEE/CKKK (E: glutamic acid), theory and experiments reveal interesting composition-driven micelle-to-fiber-to-micelle transitions. The CKK/CEE mixture exhibits three different morphologies-micelles, fibers, and lamellae-and regions of the morphology diagram showing coexistence between fibers and lamellae. MOLT calculations also provide insights into the internal organization of the assemblies and predict that the nanostructure radius can also be tuned by the composition of the mixture, in agreement with SAXS observations.
肽两亲分子（PAs）在水溶液中的自组装产生了具有丰富尺寸和形态的纳米结构，包括胶束、纤维和层状带。形态会影响PAs的生物活性，因此人们已努力通过调整其分子结构或溶液pH值来对其进行控制。然而，合成新的PAs耗时且生物医学应用将pH值限制在生理相关范围内。这项工作表明，共组装PAs二元混合物的组成是一种对超分子纳米结构的形态、尺寸和转变pH值进行合理控制的有效方法。我们结合了光散射、小角X射线散射（SAXS）、透射电子显微镜（TEM）和原子力显微镜（AFM）实验以及使用分子理论（MOLT）的理论预测，为三种相关的PA混合物构建了组成-pH形态图。对于CKK/CKKK混合物（C：棕榈酰基，K：赖氨酸），我们通过改变系统组成展示了对胶束到纤维转变pH值的精细调节。对于带相反电荷的PAs的混合物CEEE/CKKK（E：谷氨酸），理论和实验揭示了有趣的组成驱动的胶束到纤维再到胶束的转变。CKK/CEE混合物呈现出三种不同的形态——胶束、纤维和薄片——并且形态图中的区域显示了纤维和薄片之间的共存。MOLT计算还提供了对组装体内部组织的见解，并预测纳米结构半径也可以通过混合物的组成进行调节，这与SAXS观察结果一致。
