Azman Nurul Ain, Nguyen Thanh Xuan, Kah James Chen Yong
Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, Singapore.
Department of Mechanical Engineering, Vietnamese-German University, Le Lai Street, Hoa Phu Ward, Binh Duong New City 75114, Binh Duong Province, Vietnam.
J Phys Chem B. 2021 Feb 4;125(4):1181-1195. doi: 10.1021/acs.jpcb.0c09236. Epub 2021 Jan 21.
The interaction between human serum albumin (HSA) and nanoparticles (NPs) to form HSA corona has widely been studied since endogenous functions of albumin are highly attractive for drug delivery. However, a full understanding of the molecular dynamics and factors behind the formation of HSA corona, including interactions between HSA and different surface ligands and between neighboring HSA molecules, resulting in conformational change of HSA is presently lacking. Here, we assembled 14 HSA molecules around gold nanorods (AuNRs) with different surface chemistries (bare gold surface, cetyltrimethylammonium bromide (CTAB), polystyrene sulfonate (PSS), and polydiallyldimethylammonium chloride (PDADMAC)) in silico and examined the dynamics of HSA corona formation using coarse-grained molecular dynamics for 300 ns of simulation. We observed that PDADMAC, being more flexible than PSS, resulted in all HSA molecules moving toward AuNR-PDADMAC, while the instability of CTAB on AuNR resulted in fewer HSA molecules moving toward AuNR-CTAB compared to AuNR-PSS. HSA molecules around AuNR-PDADMAC also exhibited the largest conformational change in terms of their radius of gyration () and root mean square deviation (RMSD). In the absence of surface ligands, HSA molecules around the bare AuNR were susceptible to steric hindrance with conformational change observed in terms of their RMSD but not their unlike that of HSA molecules around AuNR-PDADMAC. The insights gained from the inclusion of neighboring HSA molecules in the simulation of corona formation could be more representative than examining a single adsorbed HSA molecule on AuNRs with different surface passivations.
由于白蛋白的内源性功能对药物递送具有高度吸引力，因此人们广泛研究了人血清白蛋白（HSA）与纳米颗粒（NPs）之间形成HSA冠层的相互作用。然而，目前尚缺乏对HSA冠层形成背后的分子动力学和因素的全面理解，包括HSA与不同表面配体之间以及相邻HSA分子之间的相互作用，这些相互作用会导致HSA的构象变化。在这里，我们在计算机上围绕具有不同表面化学性质（裸金表面、十六烷基三甲基溴化铵（CTAB）、聚苯乙烯磺酸盐（PSS）和聚二烯丙基二甲基氯化铵（PDADMAC））的金纳米棒（AuNRs）组装了14个HSA分子，并使用粗粒度分子动力学对300 ns的模拟过程研究了HSA冠层形成的动力学。我们观察到，PDADMAC比PSS更具柔韧性，导致所有HSA分子都向AuNR-PDADMAC移动，而CTAB在AuNR上的不稳定性导致与AuNR-PSS相比，向AuNR-CTAB移动的HSA分子更少。就回转半径（）和均方根偏差（RMSD）而言，AuNR-PDADMAC周围的HSA分子也表现出最大的构象变化。在没有表面配体的情况下，裸AuNR周围的HSA分子容易受到空间位阻的影响，从RMSD方面观察到了构象变化，但与AuNR-PDADMAC周围的HSA分子不同，其 没有变化。在冠层形成模拟中纳入相邻HSA分子所获得的见解可能比研究具有不同表面钝化的AuNRs上单个吸附的HSA分子更具代表性。
