Molecular Crystallization Controlled by pH Regulates Mesoscopic Membrane Morphology

Coassembled molecular structures are known to exhibit a large variety of geometries and morphologies. A grand challenge of self-assembly design is to find techniques to control the crystal symmetries and overall morphologies of multicomponent systems. By mixing +3 and −1 ionic amphiphiles, we assemble crystalline ionic bilayers in a large variety of geometries that resemble polyhedral cellular crystalline shells and archaea wall envelopes. We combine TEM with SAXS and WAXS to characterize the coassembled structures from the mesoscopic to nanometer scale. The degree of ionization of the amphiphiles and their intermolecular electrostatic interactions are controlled by varying pH. At low and high pH values, we observe closed, faceted vesicles with two-dimensional hexagonal molecular arrangements, and at intermediate pH, we observe ribbons with rectangular-C packing. Furthermore, as pH increases, we observe interdigitation of the bilayer leaflets. Accurate atomistic molecular dynamics simulations explain the pH-dependent bilayer thickness changes and also reveal bilayers of hexagonally packed tails at low pH, where only a small fraction of anionic headgroups is charged. Coarse-grained simulations show that the mesoscale geometries at low pH are faceted vesicles where liquid-like edges separate flat crystalline domains. Our simulations indicate that the curved-to-polyhedral shape transition can be controlled by tuning the tail density in regions where sharp bends can form the polyhedral edges. In particular, the pH acts to control the overall morphology of the ionic bilayers by changing the local crystalline order of the amphiphile tails.共组装分子结构已知可呈现多种多样的几何构型与形貌特征。自组装设计领域的一项重大挑战，在于研发可精准调控多组分体系晶体对称性与整体形貌的技术方案。本研究通过混合+3价与-1价离子两亲分子，成功制备出多种几何形态的结晶离子双层膜，其结构酷似多面体蜂窝状结晶壳层与古菌细胞壁包膜。我们结合透射电子显微镜（Transmission Electron Microscopy, TEM）、小角X射线散射（Small-Angle X-ray Scattering, SAXS）与广角X射线散射（Wide-Angle X-ray Scattering, WAXS），对介观至纳米尺度的共组装结构进行全面表征。通过调节体系pH值，可精准调控两亲分子的电离程度及其分子间静电相互作用。在低pH与高pH条件下，我们观测到具有二维六角分子排列的闭合多面囊泡；而在中等pH区间，则可观测到呈现矩形-C堆积的带状结构。此外，随着pH值升高，我们还观测到双层膜小叶的插层现象。高精度全原子分子动力学模拟不仅解释了pH依赖的双层膜厚度变化规律，还揭示了低pH条件下存在六角密排尾链的双层膜结构，此时仅少量阴离子头基带电荷。粗粒度模拟结果表明，低pH条件下的介观尺度几何结构为多面囊泡，其类液态边缘分隔着多个平坦的结晶畴域。我们的模拟结果显示，曲面向多面体的形貌转变可通过调控可形成多面体边缘的弯折区域的尾链密度来实现。具体而言，pH可通过改变两亲分子尾链的局域结晶有序性，实现对离子双层膜整体形貌的精准调控。