Li Ye, Zhang Man, Niu Xinhui, Yue Tongtao
National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China; Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China; Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
Colloids Surf B Biointerfaces. 2022 Jun;214:112467. doi: 10.1016/j.colsurfb.2022.112467. Epub 2022 Mar 18.
Nanoparticles (NPs) enter cells via multiple pathways, all of which are NP size dependent. Previous studies indicated that the clathrin-mediated endocytosis has different selectivity for the NP size, but the regulatory mechanism remains unclear and difficult to study at the molecular scale in vivo. By means of computer simulation, here we design membrane wrapping on differently sized NPs with mimic clathrin assembly at the opposite membrane side. With relatively large NPs readily wrapped by a pure membrane as manifested, clathrin modulates the process and tunes the size selectivity. Although finite curvature can be generated by cage-like clathrin assembly to facilitate membrane wrapping on relatively small NPs, the clathrin assemblage has a certain range of size, which is mismatched with larger NPs. Besides, the local membrane patch is rigidified by clathrin to increase the barrier of membrane wrapping on larger NPs. Competition of these items determines whether membrane wrapping on NPs is promoted or suppressed, and can be tuned by the NP-membrane adhesion strength, clathrin concentration, and inter-NP distance. Our results highlight the significance of complex environment in altering the nature of NP interaction with cell membranes, and are expected to help design NPs for biomedical applications requiring precise control of NP uptake or cell membrane attachment.
纳米颗粒（NPs）通过多种途径进入细胞，所有这些途径都取决于NP的大小。先前的研究表明，网格蛋白介导的内吞作用对NP大小具有不同的选择性，但其调控机制仍不清楚，且难以在体内分子水平上进行研究。通过计算机模拟，我们在此设计了在相反膜侧模拟网格蛋白组装的不同大小NP上的膜包裹。结果表明，相对较大的NP容易被纯膜包裹，而网格蛋白则调节这一过程并调整大小选择性。尽管笼状网格蛋白组装可产生有限曲率以促进相对较小NP上的膜包裹，但网格蛋白组装具有一定的大小范围，这与较大的NP不匹配。此外，网格蛋白使局部膜片硬化，从而增加了较大NP上膜包裹的屏障。这些因素的竞争决定了NP上的膜包裹是被促进还是被抑制，并且可以通过NP与膜的粘附强度、网格蛋白浓度和NP间距离来调节。我们的结果突出了复杂环境在改变NP与细胞膜相互作用性质方面的重要性，有望有助于设计用于需要精确控制NP摄取或细胞膜附着的生物医学应用的NP。
