Modeling cell membrane perturbation by molecules designed for transmembrane electron transfer

Hinks, Jamie, Wang, Yaofeng, Poh, Wee Han, Donose, Bogdan C., Thomas, Alexander W., Wuertz, Stefan, Loo, Say Chye Joachim, Bazan, Guillermo C., Kjelleberg, Staffan, Mu, Yuguang and Seviour, Thomas (2014) Modeling cell membrane perturbation by molecules designed for transmembrane electron transfer. Langmuir, 30 9: 2429-2440. doi:10.1021/la403409t

Author Hinks, Jamie
Wang, Yaofeng
Poh, Wee Han
Donose, Bogdan C.
Thomas, Alexander W.
Wuertz, Stefan
Loo, Say Chye Joachim
Bazan, Guillermo C.
Kjelleberg, Staffan
Mu, Yuguang
Seviour, Thomas
Title Modeling cell membrane perturbation by molecules designed for transmembrane electron transfer
Journal name Langmuir   Check publisher's open access policy
ISSN 0743-7463
Publication date 2014-02-05
Year available 2014
Sub-type Article (original research)
DOI 10.1021/la403409t
Open Access Status Not yet assessed
Volume 30
Issue 9
Start page 2429
End page 2440
Total pages 12
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Abstract Certain conjugated oligoelectrolytes (COEs) modify biological function by improving charge transfer across biological membranes as demonstrated by their ability to boost performance in bioelectrochemical systems. Molecular level understanding of the nature of the COE/membrane interactions is lacking. Thus, we investigated cell membrane perturbation by three COEs differing in the number of aromatic rings and presence of a fluorine substitution. Molecular dynamic. simulations showed that membrane deformation by all COEs resulted from membrane thinning as the lipid phosphate heads were drawn toward the center of the bilayer layer by positively charged COE side chains. The four-ringed COE, which most closely resembled the lipid bilayer in length, deformed the membrane the least and was least disruptive, as supported by toxicity testing (minimum inhibitory concentration (MIC) = 64 mu mol L-1) and atomic force microscopy (AFM). Extensive membrane thinning was observed from three-ringed COEs, reducing membrane thickness to <3.0 nm in regions where the COEs were located. Severe localized membrane pitting was observed when the central aromatic ring was unfluorinated, as evident from AFM and simulations. Fluorinating the central aromatic ring delocalized thinning but induced greater membrane disorder, indicated by changes in deuterium order parameter of the acyl chains. The fluorinated three-ringed compound was less toxic (MIC 4 mu mol L-1) than the nonfluorinated three-aromatic-ringed COE (MIC 2 mu mol L-1); thus, hydrophobic polar interactions resulting from fluorine substitution of OPV COEs dissipate membrane perturbations. Correlating specific structural features with cell membrane perturbation is an important step toward designing non-antimicrobial membrane insertion molecules.
Keyword Chemistry, Multidisciplinary
Chemistry, Physical
Materials Science, Multidisciplinary
Materials Science
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Advanced Water Management Centre Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 20 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 01 Mar 2014, 15:13:30 EST by Dr Bogdan C. Donose on behalf of Advanced Water Management Centre