受体特性通过受体介导的内吞作用对颗粒内化的影响,Soft Matter

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受体特性通过受体介导的内吞作用对颗粒内化的影响
Soft Matter ( IF 2.9 ) Pub Date : 2023-07-12 , DOI: 10.1039/d3sm00149k
Md Muhtasim Billah ₁ , Hua Deng ₂ , Prashanta Dutta ₁ , Jin Liu ₁

Affiliation

受体介导的内吞作用（RME）是由病毒和药物载体等生物颗粒进入细胞的高度复杂的过程。网格蛋白依赖性和无网格蛋白途径的发现使得 RME 过程更加有趣。已经开发了数值模型来促进对该过程的探索。然而，由于受体模型过于简单化，受体特性对 RME 的影响研究较少。在本文中，我们采用随机模型来系统地研究受体的机械（受体弯曲）、几何（受体长度）和生物化学（配体-受体截止）特性对有或没有网格蛋白存在的 RME 的影响。我们的模拟结果表明，受体的弯曲刚度在网格蛋白 RME 中起着重要作用。存在一个阈值，超过该阈值就不会发生颗粒内化。如果没有网格蛋白，仅通过配体-受体相互作用很难实现完全的内吞作用。较短的受体长度和较长的配体-受体反应截止促进配体-受体键的形成并促进颗粒内化。完全内化只能通过极短的受体长度和长的反应截止时间来获得。因此，很可能存在一些额外的机制来驱动无网格蛋白 RME 中的膜变形。我们的结果为 RME 提供了重要的基本见解，并在将模拟结果与实验观察结果关联起来时提供了重要的指导。

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Effects of receptor properties on particle internalization through receptor-mediated endocytosis

Receptor-mediated endocytosis (RME) is a highly complex process carried out by bioparticles, such as viruses and drug carriers, to enter cells. The discovery of both clathrin-dependent and clathrin-free pathways makes the RME process even more intriguing. Numerical models have been developed to facilitate the exploration of the process. However, the impacts of the receptor properties on RME have been less studied partially due to the oversimplifications of the receptor models. In this paper, we implement a stochastic model to systematically investigate the effects of mechanical (receptor flexure), geometrical (receptor length) and biochemical (ligand–receptor cutoff) properties of receptors, on RME with and without the existence of clathrin. Our simulation results show that the receptor's flexural rigidity plays an important role in RME with clathrin. There is a threshold beyond which particle internalization will not occur. Without clathrin, it is very difficult to achieve complete endocytosis with ligand–receptor interactions alone. A shorter receptor length and longer ligand–receptor reaction cutoff promote the formation of ligand–receptor bonds and facilitate particle internalization. Complete internalization can only be obtained with an extremely short receptor length and long reaction cutoff. Therefore, there are most likely some additional mechanisms to drive the membrane deformation in clathrin-free RME. Our results yield important fundamental insights into RME and provide crucial guidance when correlating the simulation results with experimental observations.

更新日期：2023-07-12

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