Molecular Simulation On Interaction Between Nanoparticles And Phase-separated Cell Membranes Containning Charged Lipids

Nanoparticles have many advantages,such as large surface area,small size,many active points.They have been widely used in many fields such as nanomedicine,cell imaging,optical probes and so on.In recent years,nanoparticles play an important role in the treatment of cancer as drug carriers.However,the cytotoxicity of some nanoparticles,which will cause a certain degree of damage to the cell,can not be neglected.The applications of nanoparticles are closely associated with the interactions between nanoparticles and cell membrane.Therefore,it is vital to understand the microscopic mechanism of interaction between nanoparticles and cell membranes and it is the key to develop and design nanoparticles with low toxicity and high efficiency.Grafting various biological short chains on the surface of nanoparticles is a common way to improve the efficiency of nanoparticles in many applications.Currently,there have been a great deal of experimental and theoretical studies on the interactions between different nanoparticles and cell membranes.Nevertheless,most of the previous studies focused on the interactions between nanoparticles and neutral membranes which are composed of one-component neutral lipid or in one phase.However,real cell membranes are composed of proteins and different kinds of lipids and form different phase-separated domains.The microscopic mechanism of the interaction between nanoparticles and phase-separated cell membranes are still poorly understood.In addition,there are many charged lipids in real cell membranes besides neutral lipids.These charged lipids may significantly affect the interactions between nanoparticles and cell membranes and should be carefully considered.In this thesis,using coarse-gained molecular dynamics simulation,we study the interactions between nanoparticles grafted with different biological short chains and charged phase-separated cell membranes.We set up different systems consist of nanoparticles grafted with ligands of different density and phase-separated cell membranes containing charged liquid-ordered domain or charged liquid-disordered domain.Furthermore,through calculating the potential of mean force between nanoparticle and different domains,we explain the microscopic mechanism of interactions between nanoparticles and phase-separated cell membranes containing charged liquid-ordered domain or charged liquid-disordered domain and reveal the effects of electrostatic,hydrophobic and grafting density of ligands on the interactions between nanoparticles and cell membranes in detail on molecular level.The main results are as follows.For the case of nanoparticles grafted with positive ligands and negative Ld domain,three kinds of nanoparticles with different grafting densities are adsorbed on the surface of the Lo domain finally.When the Ld domain is negative,nanoparticles grafted with ligands of high density are adsorbed on the surface of the Ld domain,while nanoparticles grafted with ligands of low density are adsorbed and embedded into the Ld domain.When grafted ligands are negative and one of the lipid domains is negative,the nanoparticles grafted with high ligand density are excluded and adsorbed on the surface of neutral domains for either the case the negative Lo domain or the case of negative Ld domain,.The nanoparticles grafted with low density are adsorbed on the boundary of two domains.For the nanoparticles grafted with both hydrophobic neutral and hydrophilic positive ligands,when the Lo domain is negative,the nanoparticles with a low grafting density of hydrophobic ligands are adsorbed on the surface of the Lo domain,while the nanoparticles with a high grafting density of hydrophobic ligands penetrate into the Ld domain.When the Ld domain is charged,all nanoparticles are adsorbed and embedded into the Ld domain.For the nanoparticles grafted with hydrophobic neutral and negative ligands,the nanoparticles with a high ratio of charged ligands are adsorbed on the boundary of the two domains for both case of Lo and Ld domain being negative,while the nanoparticles with a low ratio of charged ligands are embedded into the Ld domain.This study provides a theoretical method to modulate the interaction between nanoparticles and cell membranes.,and is also significant for designs and applications of nanoparticles in some relevant fields.