人工脂滴的构筑及其动态行为调控机制探索

The design and construction of various dynamic self-assembled systems towards the mimicking of certain life’s behaviors or functions, is now attracting more and more researchers’ attention. Among these studies, lipid droplet, is a type of dynamic multi-functional organelle in cells, and it has been confirmed that many human diseases, especially metabolic diseases were associated with it including diabetes and obesity etc. Despite of these achievements, there is still a lack of comprehensive understanding about lipid droplets including its formation, fusion, growth, as well as the dynamic regulation mechanism. While, based on chemical perspective, via the construction of artificial lipid droplets to understand the mystery of the lipid droplet is still rare. Herein, in this project, we are aiming to develop a general way to synthesize artificial lipid droplets, and then by operating the proteins located in the membrane, the constructed lipid droplets could be endowed with modulated fusion behavior, as well as enzymatic reaction-induced oscillating. In addition, by loading the building blocks into the core domain of the BSA-based microcapsules, the in situ formation of artificial lipid droplets was also investigated. Accordingly, the understanding of the dynamic mechanism of the artificial lipid droplets will contribute another view and strategy to unravel the mystery dynamic behavior of lipid droplets in life. Moreover, the established artificial lipid droplets will not only enrich the design of artificial cell models with encapsulated various artificial cellular organelles, but also as a type of oil in water microcapsules, show promising application in the field of interfacial catalytic reaction as well as transportation of different payloads within the two phases.

设计构筑动态超分子组装体系，探索模拟生命体中特定行为、功能，已引起多学科研究者们极大兴趣。其中，脂滴作为细胞内一种动态多功能细胞器与糖尿病、肥胖等多种代谢疾病直接相关，尽管其功能正逐渐被生物学家们所证实，但是其一些基本行为包括形成、融合、生长等仍然是神秘的。而从化学角度构筑人工脂滴阐明其动态行为及调控机制，该方面研究国内外鲜有报道。在此，本项目将建立一种人工脂滴构筑的普适方法，通过对其膜上蛋白质的设计实现脂滴的融合、生长等动态行为的构筑以及基于膜上酶催化反应诱导脂滴的振荡调控；利用蛋白质胶囊为模型探索微尺度限域空间内脂滴原位形成的可行性；揭示该系列动态行为机制及调控因素，进而从化学角度贡献一种认识及揭示脂滴神秘行为的新方法和新视角。此外该动态人工脂滴体系的建立，也将丰富人工细胞领域对其内部结构的多样性设计，同时该脂滴作为一种两相微胶囊结构也展现了在界面催化以及两相间物质传输等方面应用潜能。

脂滴作为细胞内一种动态多功能细胞器与糖尿病、肥胖等多种代谢疾病直接相关，尽管其功能正逐渐被生物学家们所证实，但是其一些基本行为包括形成、融合、生长等仍然是神秘的。本项目针对设计构筑动态超分子组装体系，朝向探索模拟生命体中特定行为、功能，发展了从化学角度构筑人工脂滴并阐明了其动态行为及基于酶催化驱动的调控机制。具体包括有建立了一种人工脂滴构筑的普适方法，通过对其膜上蛋白质的设计实现了脂滴的融合、生长等动态行为的构筑以及基于膜上酶催化反应诱导脂滴的振荡调控，阐明了基于物质扩散诱导的脂滴融合机制；成功利用蛋白质胶囊为模型探索了微尺度限域空间内脂滴原位形成的可行性；揭示了该系列动态行为调控因素，进而从化学角度贡献一种认识及揭示脂滴神秘行为的新方法和新视角。此外该动态人工脂滴体系的建立，也有望丰富人工细胞领域对其内部结构的多样性设计，同时该脂滴作为一种两相微胶囊结构也展现了在界面催化以及两相间物质传输等方面应用潜能。.在基金资助下，共发表项目号（21871069）标注的SCI论文27篇，包括Chem., Nat. Commun., Adv. Mater., Angew. Chem. Int. Ed.(4篇)，CCS Chem等。申请国家发明专利5项，已授权3项，培养研究生4人，博士生7人。