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Molecular dynamics simulations predict the pathways via which pristine fullerenes penetrate bacterial membranes

Molecular dynamics simulations predict the pathways via which pristine fullerenes penetrate bacterial membranes
Molecular dynamics simulations predict the pathways via which pristine fullerenes penetrate bacterial membranes
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 C60 fullerenes with bacterial membranes using the coarse-grain molecular dynamics Martini force field. We found that pristine C60 has a limited tendency to penetrate (incomplete core) Re mutant lipopolysaccharide (LPS) leaflets, but the translocation of C60 fullerenes 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 C60 into 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 C60 aggregates 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.
1520-6106
11170-11179
Hsu, Pin-Chia
4b4c8c18-752e-4ba8-a456-0fc71df1b286
Jefferies, Damien
8df97e21-8df6-4571-bfbe-3edc41e16967
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Hsu, Pin-Chia
4b4c8c18-752e-4ba8-a456-0fc71df1b286
Jefferies, Damien
8df97e21-8df6-4571-bfbe-3edc41e16967
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Hsu, Pin-Chia, Jefferies, Damien and Khalid, Syma (2016) Molecular dynamics simulations predict the pathways via which pristine fullerenes penetrate bacterial membranes. The Journal of Physical Chemistry B, 120 (43), 11170-11179. (doi:10.1021/acs.jpcb.6b06615).

Record type: Article

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 C60 fullerenes with bacterial membranes using the coarse-grain molecular dynamics Martini force field. We found that pristine C60 has a limited tendency to penetrate (incomplete core) Re mutant lipopolysaccharide (LPS) leaflets, but the translocation of C60 fullerenes 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 C60 into 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 C60 aggregates 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.

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More information

Accepted/In Press date: 5 October 2016
e-pub ahead of print date: 7 October 2016
Published date: 3 November 2016
Organisations: Faculty of Natural and Environmental Sciences

Identifiers

Local EPrints ID: 405560
URI: http://eprints.soton.ac.uk/id/eprint/405560
ISSN: 1520-6106
PURE UUID: e39540ff-1609-43fa-807a-5b8ff2f7833e
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 07 Feb 2017 16:14
Last modified: 16 Mar 2024 03:56

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Contributors

Author: Pin-Chia Hsu
Author: Damien Jefferies
Author: Syma Khalid ORCID iD

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