Dynamics of Human Serum Albumin Corona Formation on Gold Nanorods with Different Surface Ligands In Silico

Abstract

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 (R g ) 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 R g 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.

Thermodynamic and Kinetic Binding Behaviors of Human Serum Albumin to Silver Nanoparticles

“…Since albumin proteins may lose their original structure and function after adsorption on NPs surfaces, it is important to further understand how the structural integrity in albumin contributes to the efficient use of albumin as a drug carrier on NPs. Unluckily, there still lacks a good understanding about the factors influencing the interaction of HSA with NPs, particularly how surface ligands on NPs and intermolecular interactions of HSA molecules in corona formation influence the dynamics and conformation [ 15 ]. With the specific structural characteristics and physiological functions of HSA, it is usually employed as a model protein in research regarding the interaction with drug molecules, nanoparticles, and other ligands [ 16 , 17 , 18 ].…”

Molecular scale study on the interactions of biocompatible nanoparticles with macrophage membrane and blood proteins

“…According to Azman et al., [ 44 ] Rg and ΔRg give insights into the corona formation around NPs. Therefore, to deeply explore the outcomes, the dynamic of corona formation is evaluated in terms of Rg and ΔRg regarding polymer strands and blood protein in the course of the simulation and the behavior that the substances show in the blood environment and their accumulation in this simulation are quite similar to the simulation with respect to Rg and ΔRg.…”

Conjugating Ligands to an Equilibrated Nanoparticle Protein Corona Enables Cell Targeting in Serum

“…We begin the simulation by preparing a roughly 60 nm × 60 nm × 60 nm simulation box, with a spherical ∼15 nm diameter AuNP in the center. We use CHARMM-GUI webserver , to prepare the nanoparticle in atomistic configuration and convert it to the Maritini3 CG model by using the C6 type beads for each atom in the nanoparticle as discussed in previous works. , We used position restraints to prevent any changes in the nanoparticle’s configuration.…”