International Research Center for Computational Mechanics, State Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Faculty of Vehicle Engineering and Mechanics, Dalian University of Technology , Dalian 116024, P. R. China.
J Phys Chem B. 2018 Jan 11;122(1):171-180. doi: 10.1021/acs.jpcb.7b09619. Epub 2017 Dec 19.
A complete understanding of the interactions between nanoparticles (NPs) and the cell membrane is essential for the potential biomedical applications of NPs. The rotation of the NP during the cellular wrapping process is of great biological significance and has been widely observed in experiments and simulations. However, the underlying mechanisms of the rotation and their potential influences on the wrapping behavior are far from being fully understood. Here, by coupling the rotation of the NP with the diffusion of the receptors, we set up a model to theoretically investigate the wrapping pathway and the internalization rate of the rotatable NP in the receptor-mediated endocytosis. Based on this model, it is found that the endocytosis proceeds through the symmetric-asymmetric or asymmetric-symmetric-asymmetric wrapping pathway due to the bending and membrane tension competition induced rotation of NP. In addition, we show that the wrapping rate in the direction that the wrapping proceeds can be largely accelerated by the rotation. Moreover, the time to fully wrap the NP depends not only on the size and shape of the NP but also on its rotation and initial orientation. These results reveal the roles of the shape, rotation, and initial orientation of the NP on the receptor-mediated endocytosis and may provide guidelines for the design of NP-based drug delivery systems.
完全理解纳米颗粒（NPs）与细胞膜之间的相互作用对于 NPs 的潜在生物医学应用至关重要。NP 在细胞包裹过程中的旋转具有重要的生物学意义，在实验和模拟中已经广泛观察到。然而，旋转的潜在机制及其对包裹行为的潜在影响远未得到充分理解。在这里，通过将 NP 的旋转与受体的扩散相耦合，我们建立了一个模型，从理论上研究了可旋转 NP 在受体介导的胞吞作用中的包裹途径和内化速率。基于该模型，发现由于 NP 诱导的弯曲和膜张力竞争导致的旋转，内吞作用通过对称-不对称或不对称-对称-不对称的包裹途径进行。此外，我们表明，由于旋转，沿包裹进行方向的包裹速率可以大大加快。此外，完全包裹 NP 的时间不仅取决于 NP 的大小和形状，还取决于其旋转和初始方向。这些结果揭示了 NP 的形状、旋转和初始方向对受体介导的胞吞作用的作用，可能为基于 NP 的药物输送系统的设计提供指导。
