Interactions Between Amphiphilic Janus Nanoparticles And Symmetric/Asymmetric Biomembranes In Different Phases

Due to their unique physicochemical properties,nanoparticles have been widely used in drug delivery,biological detection,cell imaging,photothermal therapy and many other biomedical fields.In most of these applications,the nanoparticles usually need to interact with cell membrane.However,one of the biggest challenges in the biomedical applications of nanoparticle is their cytotoxicity and biological safety.Many nanoparticles may damage cell membranes or even kill cells.Therefore,it is very important to understand the microscopic mechanism of the interactions between nanoparticles and cell membrane so as to improve the nanoparticles' biological safety and further control the process of nanoparticle translocation through the cell membrane or nanoparticle adsorption onto the cell membrane surface.Surface functionalization of nanoparticle is an essential method to modulate the nanoparticle properties and the interactions between nanoparticles and cell membranes.The surface functionalization of nanoparticles usually includes biomolecule modification,polymer modification,small-molecule ligand modification,and surface geometric modification and so on.Recently,many attentions are paid on the amphiphilic Janus gold nanoparticle which is coated with hydrophobic ligands on one half of the surface and hydrophilic ligands on the other half.This unique surface structure makes the amphiphilic Janus nanoparticle as an ideal carrier for some drugs.Some relevant experiments showed that,compared with the nanoparticle with a homogenous surface,Janus nanoparticle can more easily produce pores in the cell membrane.However,the molecular mechanism of the interactions between amphiphilic Janus nanoparticles and cell membranes remainselusive.In this thesis,using all-atom molecular dynamics simulation,we investigated the interactions between amphiphilic Janus nanoparticles and symmetric/asymmetric lipid bilayers with different phases.The results show that,the amphiphilic Janus modification of the surface of gold nanoparticle is an effective method for modulation of the nanoparticle adsorption onto the surface of lipid bilayer or the nanoparticle penetration into the lipid bilayer.The main results of this thesis are as follows:(1)Amphiphilic Janus nanoparticle is able to easily penetrate into the symmetric lipid bilayer with a liquid-disordered(Ld)phase.Because the symmetric Lo lipid bilayer is completely composed of unsaturated DLi PC molecules which pack loosely and disorderedly in the bilayer,the nanoparticle can readily insert into it.(2)Compared with the symmetric Ld bilayer,amphiphilic Janus nanoparticle is difficult to penetrate into the symmetric lipid bilayer with a liquid-ordered(Lo)phase.The symmetric Lo bilayer consists of saturated DPPC and cholesterol with a certain molar ratio.For the symmetric Lo bilayer composed of DPPC and cholesterol with the molar ratio of7:3,we ran four simulations on this system and the results show that the nanoparticle penetrates into the bilayer in only two of the simulations while it is only adsorbed onto the surface of the bilayer in the other two simulations.For the symmetric Lo bilayer composed of 5:5 DPPC and cholesterol,in all the four replicas of simulations,the nanoparticle never penetrates into the bilayer.This is mainly because that the packing of lipids in this bilayer is very ordered and compact and the nanoparticle is very difficult to penetrate into the bilayer.(3)For the asymmetric lipid bilayers composed of a Lo leaflet and a Ld leaflet,amphiphilic Janus nanoparticle always can readily penetrate into the Lo leaflet.This is mainly because that the asymmetric bilayer has an intrinsic curvature and can spontaneously curve toward the Ld leaflet.The curvature of the bilayer can increase the spacing between the lipids,reduce the degree of the packing order of the lipids,introduce some defects between the lipids,and facilitate the penetration of the nanoparticle into thebilayer.In summary,the penetration of the amphiphilic Janus nanoparticle is mainly dominated by the ligand hydrophobicity,the packing order of lipids and the curvature of lipid bilayers.This work provides some new insights into understanding the interactions between the amphiphilic Janus nanoparticle and cell membrane from the molecular scale and some novel idea for the design of gold nanoparticle in the biomedical applications such as drug delivery.