State Key Laboratory of Tree Genetics and 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.
J Mater Chem B. 2023 Jul 12;11(27):6319-6334. doi: 10.1039/d3tb00322a.
Nanoparticles have been widely used in biomedical applications such as gene/drug delivery, molecular imaging and diagnostics. Among the physicochemical properties, shape is a vital design parameter for tuning the cell uptake of nanoparticles. However, the regulatory mechanism remains elusive due to the complexity of the cell membrane and multiple pathways of cell uptake. Therefore, in this computational study, we design and clarify cell membrane wrapping on different shaped nanoparticles (sphere, rod and disk) with a clathrin assembly to model the clathrin-mediated endocytosis, which is an important pathway of nanoparticle cell uptake. Our simulations revealed that the clathrin-mediated endocytosis is shape sensitive for nanoparticles. Spherical nanoparticles are easier to be wrapped by the membrane with the self-assembly of clathrins than the other shaped nanoparticles with the same volume, and the efficiency declines with the increase in the nanoparticle shape anisotropy. Furthermore, simulation results showed clear evidence that rotation is one of the typical characteristics determining the kinetics of clathrin-mediated endocytosis of shaped nanoparticles. Especially for rod nanoparticles with high aspect ratios, nanoparticle rotation occurs in both the invagination and wrapping stages, which is different from the case without clathrins. The size and shape mismatch between the clathrin-mediated vesicle and the nanoparticle determines how the nanoparticle rotates and is wrapped by the membrane. In addition, the wrapping time of nanoparticles depends not only on the shape of the nanoparticle but also on its initial orientation and size, the rate of clathrin self-assembly and the surface tension of the membrane. These results provide insights into the interplay between cell membrane wrapping and clathrin assembly, where the nanoparticle shape matters. Understanding the dynamics mechanism of clathrin-mediated endocytosis of nanoparticles will help to design targeted nanomedicines with an improved efficacy.
纳米颗粒已广泛应用于生物医学领域，如基因/药物传递、分子成像和诊断。在物理化学性质中，形状是调节纳米颗粒细胞摄取的重要设计参数。然而，由于细胞膜的复杂性和细胞摄取的多种途径，其调控机制仍不清楚。因此，在这项计算研究中，我们设计并阐明了不同形状的纳米颗粒（球体、棒体和圆盘）在网格蛋白组装体作用下的细胞膜包裹情况，以模拟网格蛋白介导的内吞作用，这是纳米颗粒细胞摄取的重要途径。我们的模拟结果表明，网格蛋白介导的内吞作用对纳米颗粒的形状敏感。与具有相同体积的其他形状的纳米颗粒相比，球形纳米颗粒更容易被网格蛋白自组装包裹在膜中，并且随着纳米颗粒形状各向异性的增加，效率会降低。此外，模拟结果清楚地表明，旋转是决定形状纳米颗粒网格蛋白介导的内吞动力学的典型特征之一。特别是对于高纵横比的棒状纳米颗粒，纳米颗粒在凹陷和包裹阶段都会发生旋转，这与没有网格蛋白的情况不同。网格蛋白介导的囊泡与纳米颗粒之间的大小和形状不匹配决定了纳米颗粒如何旋转和被膜包裹。此外，纳米颗粒的包裹时间不仅取决于纳米颗粒的形状，还取决于其初始取向和大小、网格蛋白自组装的速度以及膜的表面张力。这些结果为细胞细胞膜包裹与网格蛋白组装之间的相互作用提供了深入的了解，其中纳米颗粒的形状很重要。了解网格蛋白介导的内吞作用的动力学机制将有助于设计具有更好疗效的靶向纳米药物。
