Fan Zhiying, Mao Xiuhai, Zhu Meng, Hu Xingjie, Li Mingqiang, Huang Lulu, Li Jie, Maimaiti Tumala, Zuo Xiaolei, Fan Chunhai, Li Qian, Liu Mengmeng, Tian Yang
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 200241, Shanghai, China.
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
Angew Chem Int Ed Engl. 2025 Jan 2;64(1):e202413244. doi: 10.1002/anie.202413244. Epub 2024 Oct 25.
Membrane fission involves a crucial step of lipid remodeling, in which the dynamin collar constricts and severs the tubulated lipid membrane at the neck of budding vesicles. Nevertheless, the difficulty in accurately determining the rotational dynamics of live endocytotic vesicles poses a limit on the elucidation of dynamin-induced membrane remodeling for endocytotic vesicle scission. Herein, we designed a DNA-modified gold homodimer (AuHD)-based anisotropic plasmonic probe with uniform surface chemistry, minimizing orientational fluctuation within vesicle encapsulation. Using AuHDs as cargos to image the dynamics of cargo-containing vesicles during endocytosis, we showed that, prior to detachment from plasma membrane, the cargo-containing vesicles underwent multiple intermittent twists of ~4° angular orientation relative to plasma membrane with a ~0.2 s dwell time. These findings suggest that the membrane torques resulting from dynamin actions in vivo constitute the pathway to membrane fission, potentially shedding light on how dynamin-mediated lipid remodeling orchestrates membrane fission.
膜裂变涉及脂质重塑的关键步骤，其中发动蛋白环在出芽囊泡的颈部收缩并切断管状脂质膜。然而，准确确定活体内吞囊泡的旋转动力学存在困难，这限制了对发动蛋白诱导的内吞囊泡分裂的膜重塑的阐明。在此，我们设计了一种基于DNA修饰的金同型二聚体（AuHD）的各向异性等离子体探针，其具有均匀的表面化学性质，可最大限度地减少囊泡包封内的取向波动。使用AuHD作为货物来成像内吞过程中含货物囊泡的动力学，我们发现，在从质膜脱离之前，含货物囊泡相对于质膜经历了多次间歇性扭转，角度取向约为4°，停留时间约为0.2秒。这些发现表明，体内发动蛋白作用产生的膜扭矩构成了膜裂变的途径，这可能为发动蛋白介导的脂质重塑如何协调膜裂变提供线索。
