The Interaction Of C₆₀ Or Lipid Nanobubble With A Phospholipid Membrane:Molecular Dynamics Simulation

Cell is the fundamental unit of a living organism, nanoparticles must be interactions with cell membrane when applied in biomedicine. It has important enlightenment significance to reveal the mechanism of nanoparticles interacting with membrane. In recent years, with the rapid development of the computer technology and the successes in the combinations between molecular simulation and experiments, molecular simulation plays a more and more important role in nanobiology. In this thesis, we will probe the interaction between nanoparticles (C60, lipid nanobubble) and lipid bilayer using coarse-grained molecular dynamic simulations.1. C6o nanoparticles are extensively applied in medical and biological studies due to its unique properties. In order to obtain better biomedical applications, much attention should be paid to the effects of C60 on human health and the environment. In the present work, we focus on the interactions of C60 with model cell membranes. On the other hand, cholesterol plays an important role in regulating the structural properties of phospholipid membranes and further influences the permeability of molecules and nanoparticles. Here, we performed coarse-grained molecular dynamics simulations to probe the translocation of C60 across lipid bilayers with different concentrations of cholesterol molecules. The results reveal that the presence of cholesterol molecules induces lower area per lipid, larger bilayer thickness, and more ordered orientation of lipid tails. The C6o molecules spontaneously enter the bilayers and entrap in the bilayer tails region with different equilibrium z coordinates. There are only local fluctuations surrounding C60 molecules and no membrane disrupts. Computationally, the PMF profiles show slight energy barriers and have shallower energy wells with the increasing cholesterol concentration. The diffusion coefficients and permeability coefficients of C60 molecules have also been calculated. The estimated C60 permeability coefficients decrease with increasing cholesterol concentration. The reasons are the condensation effect and the reduced free volume with the addition of cholesterol.2. As the most effective type of ultrasound contrast agent, lipid nanobubble not only can provide high resolution and sensitive images of organ or tissue, but also the induced sonoporation can be used to deliver drug or gene into cells for therapeutic applications. At higher ultrasound intensities, shock wave can be generated in the fluid and jet formation can occur during the collapse of lipid nanobubble. We perform nonequilibrium simulations to investigate the effect produced by a shock wave impinging on a lipid nanobubble located next to a lipid membrane. The simulations show a planar shock wave travels in the+z direction. When the planar shock front hits the proximal side of the lipid nanobubble, the lipid nanobubble is forced to collapse and water molecules from the bubble periphery accelerate toward the center of the bubble and form a water nanojet. Since the lipid bilayer is close to the lipid nanobubble, the impact of the water nanojet cause membrane deformation. When the shock velocity is large, the deformed bilayer is hemispherical and holes form. Such poration in the membrane allows water molecules to diffuse to the hydrophobic regions. The nanojet and the deformation of membrane depend on the shock velocities and the lipid nanobubble diameter. Though a shock wave and nanobubble collapse induce the bilayer deformation, the membrane can heal. A part of the system containing a bilayer and water molecules is cut out and couple to a temperature and pressure baths. The results reveal that these holes grow larger rather quickly, reach a maximum size and then close slowly, eventually leading to a recovered planar bilayer. Since the nanopores disappear and the bilayer heals, the bilayer poration is temporary. Besides, there are water molecules transporting from one side of the bilayer to the other. Of course, the numbers of diffused water molecules are correlation with the nanobubble diameter and the shock velocity.Our work is a preliminary study on the interaction between nanoparticles and membrane. Our researches may give some guidelines to make better use of C60 and lipid nanobubble in nanomedical fields, such as drug or gene therapy and so on.