Modeling Cell Membrane Perturbation by Molecules Designed for Transmembrane Electron Transfer
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- 作者：Jamie Hinks ; Yaofeng Wang ; Wee Han Poh ; Bogdan C. Donose ; Alexander W. Thomas ; Stefan Wuertz ; Say Chye Joachim Loo ; Guillermo C. Bazan ; Staffan Kjelleberg ; Yuguang Mu ; Thomas Seviour
- 刊名：Langmuir
- 出版年：2014
- 出版时间：March 11, 2014
- 年：2014
- 卷：30
- 期：9
- 页码：2429-2440
- 全文大小：873K
- 年卷期：v.30,no.9(March 11, 2014)
- ISSN：1520-5827
文摘
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 渭mol L鈥?) 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 渭mol L鈥?) than the nonfluorinated three-aromatic-ringed COE (MIC 2 渭mol L鈥?); 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.