title: Molecular Dynamics Simulations Predict the Pathways via Which Pristine Fullerenes Penetrate Bacterial Membranes.
abstract: Carbon fullerenes are emerging as effective devices for different biomedical applications, including the transportation of nanosized drugs and extraction of harmful oxidants and radicals. It has been proposed that fullerenes could be used as novel antibacterial agents, given the realization that the nanoparticles can kill pathogenic Gram-negative bacteria. To explore this at the molecular level, we simulated C60fullerenes with bacterial membranes using the coarse-grain molecular dynamics Martini force field. We found that pristine C60has a limited tendency to penetrate (incomplete core) Re mutant lipopolysaccharide (LPS) leaflets, but the translocation of C60fullerenes into (complete core) Ra mutant LPS leaflets is not thermodynamically favored. Moreover, we showed that the permeability of the Re LPS bilayers depends sensitively on the system temperature, charge of ambient ions, and prevalence of palmitoyloleoylphosphoethanolamine (POPE) defect domains. The different permeabilities are rationalized in terms of transitory head group pore formation, which underpins the translocation of C60into the lipid core. The Re LPS lipids readily form transient micropores when they are linked with monovalent cations or when they are heated to a high temperature. POPE lipids are shown to be particularly adept at forming these transient surface cavities, and their inclusion into Re LPS membranes facilitates the formation of particularly large pores that are tunneled by C60aggregates of a significant size (∼5 nm wide). After insertion into the lipid core, the aggregates dissociate, and the disbanded nanoparticles migrate to the interface between separate POPE and LPS domains, where they weaken the boundaries between the coexisting lipid fractions and thereby promote lipid mixing.
authors.affiliation: School of Chemistry, University of Southampton , Southampton SO17 1BJ, U.K.
authors.forename: Pin-Chia
authors.initials: PC
authors.lastname: Hsu
authors.affiliation: School of Chemistry, University of Southampton , Southampton SO17 1BJ, U.K.
authors.forename: Damien
authors.initials: D
authors.lastname: Jefferies
authors.affiliation: School of Chemistry, University of Southampton , Southampton SO17 1BJ, U.K.
authors.forename: Syma
authors.initials: S
authors.lastname: Khalid
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D037741:Fullerenes / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010539:Permeability
chemical_list: D037741:Fullerenes; D008051:Lipid Bilayers; D008055:Lipids; D008070:Lipopolysaccharides; C530172:pristine (C60)