Modeling of nanoparticle-membrane interactions

Abstract

Understanding the toxicity behavior of NPs is of great importance to ensure efficient drug delivery to intracellular targets without causing cytotoxicity, to measure the long-term effects of nanoparticles (NPs), and to predict risks and hazards to humans and the environment. In this context, the current study involves (i) Coarse-grained (CG) Molecular Dynamics modeling of interactions of pristine and half polar (Janus) fullerenes with regular and peroxidized lipid membranes, (ii) cytotoxicity analysis of inorganic, organic and carbon based NPs by applying Association Rule Mining (ARM), (iii) Atomistic (AA) and CG modeling of pristine and polystyrene (PS) functionalized CNTs and their interactions with lipid bilayers. In the first part, the translocation of pure and semi-polar fullerenes along the DOPC and POPC bilayers was investigated by varying the fullerene concentration and the peroxidation level of the bilayers, and the distribution of fullerenes in the lipid bilayer was mainly explained by the degree of peroxidation and saturation level of the lipid acyl chains. In the second part, a meta-heuristic model was constructed by extracting information from the literature based on NP and cell-derived properties, as well as the conditions tested. It was determined that cytotoxicity in terms of cell viability was primarily related to the core and coating material of NPs, their synthesis pathways, and the cell type to which they were exposed. Finally, the end rings of CNT were modified at atomistic and CG level with PS and carboxyl- terminated PS (PSCOOH), which were found to be an alternative and safe material through ARM. While AA simulation results showed that PSCOOH modification was advantageous in terms of drug release, more comprehensive CG results revealed that PS chain length and grafting density should be investigated further to prevent PS blockade that may pose a threat to drug release. Increasing CNT concentration changed the structural and elastic properties of the bilayers without causing permanent membrane damage and limited the transmembrane movement of cholesterols. The penetration of the developed models to the lipid membrane occurred by non-endocytic routes.