Open AccessThe Morphology of Hydroxyapatite Nanoparticles Regulates Cargo Recognition in Clathrin-Mediated Endocytosis
Author(s) -
Cheng Zhu,
Xuejie Zhou,
Ziteng Liu,
Hongwei Chen,
Hongfeng Wu,
Xiao Yang,
Xiangdong Zhu,
Jing Ma,
Hao Dong
Publication year - 2021
Publication title -
frontiers in molecular biosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.098
H-Index - 37
ISSN - 2296-889X
DOI - 10.3389/fmolb.2021.627015
Subject(s) - endocytosis , clathrin , microbiology and biotechnology , vesicle , biophysics , receptor mediated endocytosis , pinocytosis , nanotechnology , chemistry , signal transducing adaptor protein , nanoparticle , biology , materials science , biochemistry , signal transduction , membrane , receptor
The clathrin-associated protein adaptin-2 (AP2) is a distinctive member of the hetero-tetrameric clathrin adaptor complex family. It plays a crucial role in many intracellular vesicle transport pathways. The hydroxyapatite (HAp) nanoparticles can enter cells through clathrin-dependent endocytosis, induce apoptosis, and ultimately inhibit tumor metastasis. Exploring the micro process of the binding of AP2 and HAp is of great significance for understanding the molecular mechanism of HAp’s anti-cancer ability. In this work, we used molecular modeling to study the binding of spherical, rod-shaped, and needle-shaped HAps toward AP2 protein at the atomic level and found that different nanoparticles’ morphology can determine their binding specificity through electrostatic interactions. Our results show that globular HAp significantly changes AP2 protein conformation, while needle-shaped HAP has more substantial binding energy with AP2. Therefore, this work offers a microscopic picture for cargo recognition in clathrin-mediated endocytosis, clarifies the design principles and possible mechanisms of high-efficiency nano-biomaterials, and provides a basis for their potential anti-tumor therapeutic effects.