Simulation Studies On The Interactions Between Low-dimensional Nanomaterials And Biological Cells

Cellular uptake of nanoparticles is a crucial part of the delivery and release of nanodrugs.It is more and more important to study the interactions between the nanoparticles and cell membrane as well as the inside and outside environment of the membrane.Due to the unique physico-chemical properties and desirable biocompatibility of the gold nanoparticles(AuNPs),they have been widely applied to the targeted drug delivery,cancer therapy,biological detection and other fields.However,there is still no systematical understanding of the motion mechanism of AuNPs as a carrier in the microscale.Therefore,the coarse grained molecular dynamics simulations are performed in this paper to probe the cellular uptake process of the AuNPs with ligands on the surface.Firstly,the coarse grained AuNPs model with alkanes acted as ligands are built,the terminals of ligands are replaced by positively charged coarse grained beads to model the functional groups,besides,the recently developed more realistic and complex membrane model which is comprised of 63 kinds of lipids is adopted to study the interaction between them.Simulation results suggest that the cationic AuNPs are able to pierce through the cell membrane spontaneously,and attach to the inner leaflet of the bilayer after the penetration,which matches well with the experimental results.The research of the interaction between AuNPs with the simplified membrane model is also conducted,it is found that the AuNPs can only penetrate through membrane under certain external electric field strength.Afterwards,the effect of the surface charge density of AuNPs on the AuNP-membrane interaction is investigated,the ~80% surface charged AuNPs are the most promising candidates for the potential applications in nano drug delivery by combining the high transmembrane efficiency and low cytotoxicity.The shape,size and orientation effects of the AuNPs are also studied by built the cylindrical AuNPs with different length-diameter ratios,we find that the wrapping degree of nanoparticle increases with the increase of the length to diameter ratio for cylindrical AuNPs,while the effect of initial placement of AuNPs can be neglected.Finally,previous studies reported that the abundant intracellular glutathione(GSH)is capable of replacing the cationic ligands of AuNPs.After considered the function of GSH,we conduct the successive simulations based on the above mentioned transmembrane simulation.It is found that GSH plays an important role for the transition from penetration to release of AuNPs inside the cell.Simulation results reveal that the motion mechanism of the direct penetration to release of cationic AuNPs in cellular uptake.