Modeling the membrane insertion of molecules designed for transmembrane electron transfer
Reference: Langmuir (2014) 30(9): 2429–2440

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. Structural details on the nature of the COE/membrane interactions are 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 towards the centre 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 µmol 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 localised membrane pitting was observed when the central aromatic ring was un-fluorinated, as evident from AFM and simulations. Fluorinating the 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 µmol L-1) than the non-fluorinated three-aromatic ringed COE (MIC 2 µmol L-1), thus hydrophobic polar interactions resulting from fluorine substitution of OPV COESs dissipate membrane perturbations. Correlating specific structural features with cell membrane perturbation is an important step towards designing non anti-microbial membrane insertion molecules.


Hinks J., Wang Y., Poh W. H., Donose B. C., Thomas A. W., Wuertz S., Loo S. C. J., Bazan G. C., Kjelleberg S. L. A., Mu Y. and Seviour T. W.

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Hinks J., Wang Y., Poh W. H., Donose B.C., Thomas A.W., Wuertz S., Loo J. S. C., Bazan G. C., Kjelleberg S., Mu Y., Seviour T. W.