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Monitoring the Orientational Changes of Alamethicin during Incorporation into Bilayer Lipid Membranes
Citation key ISI:000425474800016
Author Forbrig, Enrico and Staffa, Jana K. and Salewski, Johannes and Mroginski, Maria Andrea and Hildebrandt, Peter and Kozuch, Jacek
Pages 2373-2385
Year 2018
ISSN 0743-7463
DOI 10.1021/acs.langmuir.7b04265
Address 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Volume 34
Number 6
Month FEB 13
Abstract Antimicrobial peptides (AMPs) are the first line of defense after contact of an infectious invader, for example, bacterium or virus, with a host and an integral part of the innate immune system of humans. Their broad spectrum of biological functions ranges from cell membrane disruption over facilitation of chemotaxis to interaction with membrane-bound or intracellular receptors, thus providing novel strategies ``to overcome bacterial resistances. Especially, the clarification of the mechanisms and dynamics of AMP incorporation into bacterial membranes is of high interest, and different mechanistic models are still under discussion. In this work, we studied the incorporation of the peptaibol alamethicin (ALM) into tethered bilayer lipid membranes on electrodes in combination with surface-enhanced infrared absorption (SEIRA) spectroscopy. This approach allows monitoring the spontaneous and potential-induced ion channel formation of ALM in situ. The complex incorporation kinetics revealed a multistep mechanism that points to peptide peptide interactions prior to penetrating the membrane and adopting the transmembrane configuration. On the basis of the anisotropy of the backbone amide I and II infrared absorptions determined by density functional theory calculations, we employed a mathematical model to evaluate ALM reorientations monitored by SEIRA. spectroscopy. Accordingly, ALM was found to adopt inclination angles of ca. 69 degrees-78 degrees and 21 degrees in its interfacially adsorbed and transmembrane incorporated states, respectively. These orientations can be stabilized efficiently by the dipolar interaction with lipid head groups or by the application of a potential gradient. The presented potential-controlled mechanistic study suggests an N-terminal integration of ALM into membranes as monomers or parallel oligomers to form ion channels composed of parallel oriented helices, whereas antiparallel oligomers are barred from intrusion.
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