Modeling cell membrane perturbation by molecules designed for transmembrane electron transfer.
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 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 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 μmol L(-1)) than the nonfluorinated three-aromatic-ringed COE (MIC 2 μmol 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.
Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University , Singapore 637551.
Jamie
J
Hinks
Yaofeng
Y
Wang
Wee Han
WH
Poh
Bogdan C
BC
Donose
Alexander W
AW
Thomas
Stefan
S
Wuertz
Say Chye Joachim
SC
Loo
Guillermo C
GC
Bazan
Staffan
S
Kjelleberg
Yuguang
Y
Mu
Thomas
T
Seviour
D002462:Cell Membrane / Q000737:chemistry*; D004573:Electrolytes / Q000737:chemistry; D004579:Electron Transport; D004926:Escherichia coli / Q000737:chemistry / Q000166:cytology; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*
D004573:Electrolytes; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; C483858:phosphatidylethanolamine