Li Long, Zhang Yudie, Wang Jizeng
Key Laboratory of Mechanics on Disaster and Environment in Western China, Ministry of Education, College of Civil Engineering and Mechanics, Lanzhou University, Lanzhou, Gansu 730000, People's Republic of China.
R Soc Open Sci. 2017 May 31;4(5):170063. doi: 10.1098/rsos.170063. eCollection 2017 May.
Biophysical-factor-dependent cellular uptake of nanoparticles (NPs) through receptor-diffusion-mediated endocytosis bears significance in pathology, cellular immunity and drug-delivery systems. Advanced nanotechnology of NP synthesis provides methods for modifying NP surface with different ligand distributions. However, no report discusses effects of ligand distribution on NP surface on receptor-diffusion-mediated cellular uptake. In this article, we used a statistical dynamics model of receptor-diffusion-mediated endocytosis to examine ligand-distribution-dependent cellular uptake dynamics by considering that ligand-receptor complexes drive engulfing to overcome resistance to membrane deformation and changes in configuration entropy of receptors. Results showed that cellular internalization of NPs strongly depended on ligand distribution and that cellular-uptake efficiency of NPs was high when ligand distribution was within a range around uniform distribution. This feature of endocytosis ensures robust infection ability of viruses to enter host cells. Interestingly, results also indicated that optimal ligand distribution associated with highest cellular-uptake efficiency slightly depends on distribution pattern of ligands and density of receptors, and the optimal distribution becomes uniform when receptor density is sufficiently large. Position of initial contact point is also a factor affecting dynamic wrapping. This study explains why most enveloped viruses present almost homogeneous ligand distribution and is useful in designing controlled-release drug-delivery systems.
通过受体扩散介导的内吞作用，生物物理因素依赖的纳米颗粒（NPs）细胞摄取在病理学、细胞免疫和药物递送系统中具有重要意义。先进的NP合成纳米技术提供了用不同配体分布修饰NP表面的方法。然而，尚无报告讨论NP表面配体分布对受体扩散介导的细胞摄取的影响。在本文中，我们使用受体扩散介导的内吞作用的统计动力学模型，通过考虑配体-受体复合物驱动吞噬以克服对膜变形的阻力和受体构象熵的变化，来研究配体分布依赖的细胞摄取动力学。结果表明，NP的细胞内化强烈依赖于配体分布，并且当配体分布在均匀分布周围的范围内时，NP的细胞摄取效率很高。这种内吞作用的特征确保了病毒进入宿主细胞的强大感染能力。有趣的是，结果还表明，与最高细胞摄取效率相关的最佳配体分布略微取决于配体的分布模式和受体的密度，并且当受体密度足够大时，最佳分布变为均匀分布。初始接触点的位置也是影响动态包裹的一个因素。本研究解释了为什么大多数包膜病毒呈现几乎均匀的配体分布，并且对设计控释药物递送系统有用。
