Role of Nanoparticle Geometry in Endocytosis: Laying Down to Stand Up
Role of Nanoparticle Geometry in Endocytosis: Laying Down to Stand Up
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DOI：
10.1021/nl402628n
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发表时间：
2013-09-01
期刊：
影响因子：
10.8
通讯作者：
Zhang, Sulin
中科院分区：
文献类型：
--
作者：
Huang, Changjin;Zhang, Yao;Zhang, Sulin
纳米颗粒（NP）在靶向疾病诊断和治疗方面具有广阔的前景。尽管纳米粒子生物缀合物的仿生设计取得了相当大的进展，但纳米粒子大小和形状在内吞作用中的作用仍不完全清楚。使用有效的粗粒度分子动力学（CGMD）模型，我们模拟了受体介导的各种尺寸和形状的纳米粒子的内吞作用。我们的模拟表明，纳米粒子的大小和形状均可调节内吞作用的动力学。对于球形纳米粒子，存在一个最佳尺寸，在该尺寸下内吞作用所需的时间最短。对于在膜平面上具有初始直立对接位置的球形纳米粒子，内吞作用通过躺下然后站立的顺序进行。自由能分析表明，纳米颗粒的大小主要决定内吞作用能否完成，而纳米颗粒的形状打破了曲率能量景观的对称性，从而决定了内吞途径和进入角度。这些发现揭示了基于 NP 的诊断和治疗药物的合理设计，并改善了细胞靶向性。
Nanoparticles (NPs) hold great promises for targeted disease diagnosis and therapy. Despite considerable progress in biomimetic design of NP-bioconjugates, the roles of NP size and shape in endocytosis are still not fully understood. Using an efficient coarse-grained molecular dynamics (CGMD) model, we simulate receptor-mediated endocytosis of NPs of various sizes and shapes. Our simulations demonstrate that both NP size and shape modulate the kinetics of endocytosis. For spherical NPs, there exists an optimal size at which endocytosis takes the shortest time. For a spherocylindrical NP with the initial upright docking position on the membrane plane, endocytosis proceeds through a laying-down-then-standing-up sequence. A free energy analysis reveals that NP size primarily determines whether endocytosis can complete, while NP shape breaks the symmetry of curvature energy landscape and hence dictates the endocytic pathway and the angle of entry. The findings shed light on the rational design of NP-based diagnostic and therapeutic agents with improved cellular targeting.