title: Computational simulations of the interaction of lipid membranes with DNA-functionalized gold nanoparticles.
abstract: We develop a shape-based coarse-grained (SBCG) model for DNA-functionalized gold nanoparticles (DNA-Au NPs) and use this to study the interaction of this potential antisense therapeutic with a lipid bilayer model of a cell membrane that is also represented using a coarse-grained model. Molecular dynamics simulations of the SBCG model of the DNA-Au NP show structural properties which coincide with our previous atomistic models of this system. The lipid membrane is composed of 30% negatively charged lipid (1,2-dioleoyl-sn-glycero-3-phosphoserine, DOPS) and 70% neutral lipid (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) in 0.15 M sodium chloride solution. Molecular dynamics (MD) simulations of the DNA-Au NP near to the lipid bilayer show that there is a higher density of DOPS than DOPC near to the DNA-Au NP since sodium counterions are able to have strong electrostatic interactions with DOPS and the DNA-Au NP at the same time. Using a steered MD simulation, we show that this counterion-mediated electrostatic interaction between DNA-Au NP and DOPS stabilizes the DNA-Au NP in direct contact with the lipid. This provides a model for interaction of DNA-Au NPs with cell membranes that does not require protein mediation.
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL, USA.
authors.forename: One-Sun
authors.initials: OS
authors.lastname: Lee
authors.forename: George C
authors.initials: GC
authors.lastname: Schatz
mesh_terms: D004247:DNA / Q000378:metabolism*; D006046:Gold / Q000737:chemistry*; D008051:Lipid Bilayers / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D012964:Sodium / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C042511:1,2-dioleoylphosphatidylserine; D006046:Gold; D004247:DNA; D012964:Sodium; C017251:1,2-oleoylphosphatidylcholine