Lipids self-assemble into diverse supramolecular structures that exhibit thermotropic and/or lyotropic behavior. Lyotropic mesophases, where membranes conform to periodic minimal surfaces dividing two nonpenetrating aqueous subspaces, are arguably one of the most intriguing phases of lipid materials. Traditional 3D bicontinuous cubic lipid materials appear as a polycrystal of varying degrees of order. When exposed to water, the properties of the molecular building blocks of the membrane determine specific swelling limits setting the lattice dimensions at about 15 nm. This limited swelling severely impairs their application as delivery vehicles of large drugs or as matrices for guiding protein crystallization. We report the discovery of self-assembly strategies leading to the emergence of lipid bicontinuous single crystals with unprecedented swelling capacity. The conventional strategy to increase unit cell size is tweaking membrane composition to include charged building blocks, a process to achieve electrostatic-driven swelling. In this paper, we demonstrate that controlling self-assembly external conditions when coupled to membrane composition yields 3D bicontinuous cubic phases that swell up to lattice dimensions of 68 nm. Importantly, and contrary to what is perceived for soft lyotropic materials in general, the self-assembly methodology enables the development of large super-swelled monocrystals. Utilizing small-angle X-ray scattering and cryoelectron microscopy, we underpin three crucial factors dictating the stabilization of super-swelled lipid bicontinuous cubic single crystals: (i) organic solvent drying speed, (ii) membrane charge density, and (iii) polyethylene glycol-conjugated lipids amount.

中文翻译：

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超膨胀溶致单晶

脂质自组装成表现出热致和/或溶致行为的各种超分子结构。溶致中间相是膜材料最吸引人的相之一，其中膜符合划分两个不渗透的水性亚空间的周期性最小表面。传统的3D双连续立方脂质材料显示为不同顺序的多晶。当暴露于水时，膜分子构建模块的特性决定了特定的溶胀极限，从而将晶格尺寸设置为约15 nm。这种有限的溶胀严重损害了它们作为大型药物的输送载体或作为指导蛋白质结晶的基质的应用。我们报告发现自组装策略的发现导致脂质双连续单晶具有空前的溶胀能力。增加单位晶胞尺寸的常规策略是调整膜组成，使其包含带电的结构单元，这是实现静电驱动溶胀的一种方法。在本文中，我们证明了当控制自组装外部条件与膜成分耦合时，会产生3D双连续立方相，该相膨胀到68 nm的晶格尺寸。重要的是，与通常认为的软溶致材料相反，自组装方法使大超膨胀单晶的发展成为可能。利用小角度X射线散射和低温电子显微镜，i）有机溶剂的干燥速度，（ii）膜电荷密度，和（iii）聚乙二醇缀合的脂质的量。