Permeation of nanoparticles through a model membrane: CG-MD Simulations Studies
thesisposted on 2015-02-22, 00:00 authored by Bo Song
How nanoparticles interact with biological membranes and the structural and mechanical properties of membranes during the nanoparticle permeation are of significant importance in determining the toxicity of nanoparticles as well as their potential applications in phototherapy, imaging and gene/drug delivery. In this work, coarse-grained molecular dynamics (CG-MD) simulations are carried out to explore the permeation characteristics of nanoparticles through a model membrane as well as the structural and mechanical properties of the membrane. We study gold nanoparticles as our model nanoparticles and a self-assembled DPPC lipid bilayer as our model membrane. A series of simulations are performed to validate the coarse-grained model for nanoparticles and lipid membrane. We start with various sizes of nanocrystals (bare nanoparticles) and then compare the differences in permeation behaviors between bare nanoparticles with ligand-coated nanoparticles with various ligand lengths to provide insights into how the ligands affect the permeation process. After that, CG-MD is applied to investigate the water penetration, ion transport and lipid molecule flip-flop phenomenon during nanoparticle permeation. The effect of ion concentration, pressure differential across the membrane, nanoparticle size and permeation velocity have been examined in this work. Finally, CG-MD is implemented to explore a method for the calculation of membrane compressibility. Membrane behavior for conditions not studied experimentally is also predicted by our method. The findings described in our work will lead to a better understanding of nanoparticle permeation process, nanoparticle-lipid membrane interactions, membrane deformation and should help in developing more efficient nanocarrier drug delivery systems while avoiding cell cytotoxicity.