Effect of concentration of PEG coated gold nanoparticle on lung surfactant studied with coarse-grained molecular dynamics simulations
Graphical abstract
Introduction
Nanomaterials have huge potential application value in biomedical research because of the special physical and chemical properties of nanomaterials structure, including light therapy [1], photoacoustic imaging [2], the early diagnosis of cancer [3], drug transport [4] and tissue engineering [5], etc. At present, the nanomaterials has been applied to electronic components, paint, sports equipment, cosmetics, food additives, and many other commercial products [6]. The nano-biological interface problems have been researched to promote the safety of nanoparticles, which is of great significance for biomedical applications [7]. Among them, nanoparticle-cell membrane, nanoparticle-protein and other biomolecular interactions have already been the focus of the research of nanoparticles. However, obtaining kinetic information about interactions at the molecular level has been an important challenge. In recent years, computer simulation technology has been widely used to study the dynamics of the action of biomolecules, nanoparticles and biomolecules, and closely combined with experiments to explore the nano-biological interface problem [[8], [9], [10], [11], [12]].
Gold nanoparticles (AuNPs) have potential applications in bio-imaging, disease detection, drug delivery, and diagnostic purposes due to their biocompatibility, low-toxicity, and easy translocation properties [[13], [14], [15]]. AuNPs are widely used as drug delivery after modifying their surfaces by the attachment biomolecule ligands [[16], [17], [18], [19]]. Modelling research have shown more and more interests on the AuNPs and investigation of their toxicity, size, shape and surfaces modification has been proposed [[20], [21], [22], [23], [24], [25]].
Surface properties such as hydrophilicity, surface charge, and surface modification can determine the behavior of nanoparticles in vivo, in vitro and in the environment [26,27]. The surface properties of nanoparticles also play an important role in the interaction between nanoparticles and cell membranes [9]. The surface modification design of gold nanoparticles with polymer can endow them with some properties of macromolecular system. It is well known that the non-specific adsorption of proteins is a very important problem in the application of nanomaterials in vivo. In order to resist the absorption of proteins effectively, some hydrophilic polymers, such as polyethylene glycol (PEG), are usually modified on the surface of nanomaterials. However, the antifouling and stability of PEG are affected by many factors, including chain length and surface graft density etc. Walkey et al. [28]. have shown that when PEG grafting density is low, the surface of gold nanoparticles will still absorb a large number of proteins, and with the surface grafting density, the adsorption behavior of proteins will also show significant differences, leading to different interactions with cells. PEG can be chemically coupled with polylactic acid (or lactic acid-glycolic acid copolymer) and polyamino acids to form a copolymer containing PEG block, and then nanoparticles can be prepared by emulsification, solvent volatilization or micelles. Physical adsorption methods such as hydrophobic bond adsorption or electrostatic binding can also be utilized.
The relative molecular mass, coating thickness and density of PEG have obvious effects on the long-cycle effect [29]. The coat thickness of poly (lactic acid) nanoparticles modified with PEG 5000 or PEG 20000 was about 4.3 nm and 7.8 nm, respectively. The former could more effectively avoid the phagocytes of liver macrophages, and the effect of both was better than that of poloxam 188. In PEG modification, the particle size of nanoparticles will affect the flexibility of PEG chain. Smaller particle size usually corresponds to stronger chain activity and flexibility, so it is not easy to be recognized by phagocytes. Calvo et al. [30] found that PHDCA(PEGylated cyanoacrylate nanoparticles) could penetrate the blood-brain barrier and increase the concentration of PHDCA in the brain without affecting the permeability of the blood-brain barrier, which can extend the circulation time of nanoparticles in vivo and improve the brain targeting of drugs.
Li [31] had research on different hydrophilic nanoparticles in electrically neutral DPPC phospholipids bilayer differences of the process and found that a certain size of hydrophobic nanoparticles can get through the way of the free diffusion across the membrane, while hydrophilic nanoparticles tended to remain on the surface of lipid membrane, which indicate that the endocytosis mechanism of cell is an energy-mediated process. By contrast, Ding et al. [32] used amphoteric molecules to adsorb on the surface of hydrophilic nanoparticles by non-covalent adsorption, and proved by simulation that this method could realize the transmembrane diffusion of hydrophilic nanoparticles. Li et al. [33] studied the interaction between hydrophilic nanoparticles with different surface charge properties and electrically neutral DPPC phospholipids bilayer. The results showed that positively charged nanoparticles adsorbed on the surface of the membrane could inhibit themselves from being further coated by the phospholipids membrane, while negatively charged nanoparticles on the surface could promote the coating of the membrane. With the increase of surface charge density, the degree of membrane encapsulation particles also increases gradually, so as to realize the non-specific endocytic transmembrane process. Ding [34] investigated the conditions of nanoparticles modified with different ligands, and found that the strength, ligand density, ligand length, and ligand hardness could all strongly affect the receptor-mediated endocytosis process. The longer ligands promoted the adsorption of the nanoparticles to the phospholipids membrane but prevented their endocytosis across the membrane, while the higher ligand density and hardness promoted the endocytosis of the nanoparticles.
Sheikh [35] performed molecular dynamics simulations to understand the interactions between bare AuNPs and LS monolayer, they found that NP affects the structure and packing of the lipids by disordering lipid tails and impede the normal biophysical function of the lung.
Recent computational studies [36,37] have highlighted that the LS proteins adsorb quickly on the NP surface and mediate the protein corona formation by directly interacting with lipids. In this paper, we have had a research on the interactions between PEG coated AuNPs and LS monolayers at two different area per lipids (APLs) using CGMD(Coarse-grained molecular dynamics) simulations. We used PEG coated AuNPs with concentration of 0.1%, 0.28%, 0.58%, 0.88% of AuNPs/lipids, and diameter of gold core is 3 nm, The AuNPs with different concentration interact with the LS monolayers and as a consequence can affect the efficacy of nanoparticle-based systems for the purpose of delivery of drugs.
Section snippets
Methods
Coarse-grained (CG) models can be utilized to simulate the larger systems as described in this work, which can be performed at a larger length scale and several magnitude faster than atomistic MD simulations [ [[38], [39], [40]]. The CG model is based on the Martini force field and has been widely used to simulate biomolecules. The Martini model uses a four-to-one mapping, i.e. on average four heavy atoms and associated hydrogens are represented by a single interaction center.
The Martini force
Effect of AuNP concentration on LS monolayer surface tension
APL is the area occupied by a single phospholipids in the lipid monolayer plane. The APL is calculated by following formula:where a and b are the length and width of the lipid monolayer plane, N is the total number of lipid molecules in the system. On the one hand, the APL value can be used to indicate the degree of density of horizontal DPPC subdivision in the system. On the other hand, the variation of DPPC subdivision over time can be used to determine whether the system reaches
Conclusion
In this work, we studied the effect of PEG coated AuNPs with different concentration on simplified LS monolayer at two different APLs using coarse-grained molecular dynamics simulation. It was found that at high concentrations of AuNPs, AuNPs inhibited the ability of the LS monolayer to achieve normal surface tension during respiration, which results in increased surface tension at the air-water interface. In addition, AuNPs concentration also affects the ordered parameters of the lipid tail
Declaration of Competing Interest
None.
Acknowledgement
This paper is supported by Key Project of Natural Science Foundation of China (Grant No. 11832011), Tianjin Excellent Special Correspondent Project (Grant No. 16JCTPJC53100) and Hebei Natural Science Foundation (Grand No. A2020202015).
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