Zhang Yudie, Li Long, 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 730000, China.
Membranes (Basel). 2021 Dec 19;11(12):993. doi: 10.3390/membranes11120993.
Nanoparticle (NP)-cell interaction mediated by receptor-ligand bonds is a crucial phenomenon in pathology, cellular immunity, and drug delivery systems, and relies strongly on the shape of NPs and the stiffness of the cell. Given this significance, a fundamental question is raised on how the ligand distribution may affect the membrane wrapping of non-spherical NPs under the influence of cytoskeleton deformation. To address this issue, in this work we use a coupled elasticity-diffusion model to systematically investigate the role of ligand distribution in the cytoskeleton-associated endocytosis of ellipsoidal NPs for different NP shapes, sizes, cytoskeleton stiffness, and the initial receptor densities. In this model, we have taken into account the effects of receptor diffusion, receptor-ligand binding, cytoskeleton and membrane deformations, and changes in the configuration entropy of receptors. By solving this model, we find that the uptake process can be significantly influenced by the ligand distribution. Additionally, there exists an optimal state of such a distribution, which corresponds to the fastest uptake efficiency and depends on the NP aspect ratio and cytoskeleton stiffness. We also find that the optimal distribution usually needs local ligand density to be sufficiently high at the large curvature region. Furthermore, the optimal state of NP entry into cells can tolerate slight changes to the corresponding optimal distribution of the ligands. The tolerance to such a change is enhanced as the average receptor density and NP size increase. These results may provide guidelines to control NP-cell interactions and improve the efficiency of target drug delivery systems.
由受体 - 配体键介导的纳米颗粒（NP）与细胞的相互作用是病理学、细胞免疫和药物递送系统中的关键现象，并且强烈依赖于纳米颗粒的形状和细胞的硬度。鉴于此重要性，一个基本问题被提出：在细胞骨架变形的影响下，配体分布如何影响非球形纳米颗粒的膜包裹。为了解决这个问题，在这项工作中，我们使用一个耦合弹性 - 扩散模型，系统地研究配体分布在不同纳米颗粒形状、尺寸、细胞骨架硬度和初始受体密度情况下，在椭圆形纳米颗粒的细胞骨架相关内吞作用中的作用。在这个模型中，我们考虑了受体扩散、受体 - 配体结合、细胞骨架和膜变形以及受体构象熵变化的影响。通过求解这个模型，我们发现摄取过程会受到配体分布的显著影响。此外，存在这样一种分布的最优状态，它对应最快的摄取效率，并且取决于纳米颗粒的纵横比和细胞骨架硬度。我们还发现最优分布通常需要在大曲率区域局部配体密度足够高。此外，纳米颗粒进入细胞的最优状态能够容忍配体相应最优分布的轻微变化。随着平均受体密度和纳米颗粒尺寸的增加，对这种变化的耐受性增强。这些结果可能为控制纳米颗粒与细胞的相互作用以及提高靶向药物递送系统的效率提供指导。
