Atomistic simulations of anionic Au144(SR)60 nanoparticles interacting with asymmetric model lipid membranes

Abstract

Experimental observations indicate that the interaction between nanoparticles and lipid membranes varies according to the nanoparticle charge and the chemical nature of their protecting side groups. We report atomistic simulations of an anionic Au nanoparticle (AuNP(-)) interacting with membranes whose lipid composition and transmembrane distribution are to a large extent consistent with real plasma membranes of eukaryotic cells. To this end, we use a model system which comprises two cellular compartments, extracellular and cytosolic, divided by two asymmetric lipid bilayers. The simulations clearly show that AuNP(-) attaches to the extracellular membrane surface within a few tens of nanoseconds, while it avoids contact with the membrane on the cytosolic side. This behavior stems from several factors. In essence, when the nanoparticle interacts with lipids in the extracellular compartment, it forms relatively weak contacts with the zwitterionic head groups (in particular choline) of the phosphatidylcholine lipids. Consequently, AuNP(-) does not immerse deeply in the leaflet, enabling, e.g., lateral diffusion of the nanoparticle along the surface. On the cytosolic side, AuNP(-) remains in the water phase due to Coulomb repulsion that arises from negatively charged phosphatidylserine lipids interacting with AuNP(-). A number of structural and dynamical features resulting from these basic phenomena are discussed. We close the article with a brief discussion of potential implications.

Ligand-modulated interactions between charged monolayer-protected Au144(SR)60gold nanoparticles in physiological saline

“…For this reason, the interactions between AuNPs and biologically relevant molecules and aggregates such as those in cell membranes have been studied using both in vitro/vivo 1-7 and in silico 8-11 experiments. Other interaction partners of AuNPs considered in the literature include amyloids, 12 viruses, 13 bacteria, 14 proteins, 15, 16 and DNA.…”

Simulating the interaction of lipid membranes with polymer and ligand-coated nanoparticles

“…Considering the limitations in current CG models [53], atomistic models should be preferred, in principle, for the study of charged NPs. Akola and Vattulainen used all-atom simulations to investigate the initial stages of Au NP interaction with asymmetric lipid membranes as a function of NP charge [54,55]. They showed that cationic NPs bind spontaneously to both negatively charged and neutral (zwitterionic) lipid membranes, but binding to neutral membranes requires overcoming a 12 kJ/mol free energy barrier.…”

Molecular dynamics simulations on the effect of size and shape on the interactions between negative Au18(SR)14, Au102(SR)44 and Au144(SR)60 nanoparticles in physiological saline

“…[28] With regard to biomedical applications, a desirable property of gold nanoparticles is their ability to aggregate reversibly into nanoclusters of controlled size when placed in a special solution, and to dissociate back into individual nanoparticles when introduced into the body. [29, 30, 31, 32] Finally, we compare the binding affinity of Au 18 with those of Au 102 [33] and Au 144 [34, 35, 36, 37, 38, 39, 40, 32], functionalized by the same ligand under the same near-physiological conditions.…”