Role of Surface Ligands in Nanoparticle Permeation through a Model Membrane: A Coarse‐grained Molecular Dynamics Simulations Study

How nanoparticles interact with biological membranes is of significant importance in determining the toxicity of nanoparticles as well as their potential applications in phototherapy, imaging and gene/drug delivery. It has been shown that such interactions are often determined by nanoparticle physicochemical factors such as size, shape, hydrophobicity and surface charge density. Surface modification of the nanoparticle offers the possibility of creating site‐specific carriers for both drug delivery and diagnostic purposes. In this work, we use coarse‐grained molecular dynamic simulations to explore the permeation characteristics of ligand‐coated nanoparticles through a model membrane. We compare permeation behaviors of ligand‐coated nanoparticles with bare nanoparticles to provide insights into how the ligands affect the permeation process. A series of simulations is carried out to validate a coarse‐grained model for nanoparticles and lipid membrane system. The minimum driving force for nanoparticles to penetrate the membrane and the mechanism of nanoparticle‐membrane interaction were investigated. The potential of mean force profile, nanoparticle velocity profile, force profile and density profiles (planar and radial) were obtained to explore the nanoparticle permeation process. The structural properties of both nanoparticles and lipid membrane during the permeation, which are of considerable fundamental interest, are also studied in our work. The findings described in our work will lead to a better understanding of nanoparticle‐lipid membrane interactions and cell cytotoxicity and help develop more efficient nanocarrier systems for intracellular delivery of therapeutics.