Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058.
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323.
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15378-15385. doi: 10.1073/pnas.1904868116. Epub 2019 Jul 15.
Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.
使用非天然成分重建活细胞的功能是自然科学面临的重大挑战之一。球形组装体（称为囊泡）的区室化、封装和表面修饰是重建合成细胞的早期关键步骤。在这里，我们报告说，由两亲性 Janus 树状大分子自组装而成的囊泡（称为树状大分子囊泡）可以封装高浓度的疏水性成分，并且比由磷脂成分组装而成的市售隐形脂质体更有效。多层洋葱状树状大分子囊泡显示出特别高的载运低分子量化合物甚至折叠蛋白质的能力。两亲性 Janus 树状大分子与与两亲性 Janus 树状大分子偶联的金属螯合配体共组装生成树状大分子囊泡，这些囊泡在其外围以定向的方式选择性地展示折叠蛋白质。还证明了将核酸固定到树状大分子囊泡表面的模块化策略。这些发现增强了树状大分子囊泡作为多功能生物膜模拟物的功能能力。
