带电纳米颗粒与相分离的带电生物膜之间相互作用的分子模拟

纳米颗粒在纳米医药、细胞成像等领域有着非常广泛的应用,深入理解纳米颗粒与生物膜之间相互作用的微观机制是纳米颗粒合成与应用的重要基础.本文采用粗粒化分子动力学模拟的方法研究了带电配体包裹的金纳米颗粒与相分离的带电生物膜之间的相互作用.结果表明,通过改变金纳米颗粒表面的配体密度、配体带电种类和比例,以及膜内带电脂分子的种类,可以方便地调控纳米颗粒在膜表面或膜内停留的位置和状态.进一步从自由能的角度分析了带电纳米颗粒与带电生物膜之间相互作用的微观物理机制.本文对纳米粒子在纳米医药、细胞成像等领域的应用具有一定的理论参考意义.

Molecular simulation of interaction between charged nanoparticles and phase-separated biomembranes containning charged lipids

Nanoparticles have been widely used in many fields such as nanomedicine and cell imaging. Understanding the microscopic mechanism of the interaction between nanoparticles and biomembranes is very vital for the synthesis and applications of nanoparticles. In this paper, using coarse-grained molecular dynamics simulation, we study the interaction between nanoparticles coated with fully or partially charged ligands and phase-separated biomembranes containing charged lipids. The results show that the final positions or states of nanoparticles on/in the biomembranes can be readily modulated by varying the grafting density, ratio, and type of charged ligands as well as the type of charged lipids. For the nanoparticle with a highly hydrophilic surface, the nanoparticle prefers to be adsorbed on the surface of the biomembrane. In this case, the electrostatic interaction determines that the nanoparticle is adsorbed on the surface of liquid-ordered domain or the surface of liquid-disordered domain. For the nanoparticle with a (partially) hydrophobic surface, the nanoparticle tends to penetrate into the lipid bilayer from the liquid-disordered domain. In this case, the hydrophobicity of the nanoparticle plays a crucial role in the penetrating of the nanoparticle. The hydrophilicity or hydrophobicity of the nanoparticle is affected by the ratio between the charged and neutral ligands, the grafting density of the charged ligands, and the ionic concentration in the system. Furthermore, the microscopic mechanism of the interaction between charged nanoparticles and charged biomembranes is revealed by using the potential of mean force between nanoparticles and lipid domains. The potential of mean force shows that none of the (partially) charged nanoparticles can spontaneously penetrate into the liquid-ordered domain due to a high free energy barrier but they can spontaneously penetrate into the liquid-disordered domain with a certain probability. However, due to the limitation of the simulation time and the number of sampling of the simulations, only some of the partially hydrophobic nanoparticles which are not initially adsorbed onto the surface of liquid-ordered domain are found to finally penetrate into the liquid-disordered domain in this work. This work yields some theoretical insights into the application of nanoparticles in nanomedicine, cell imaging, etc.