Abstract
The mechanism of membrane permeabilization by the antimicrobial peptide distinctin was investigated by using two different mercury-supported biomimetic membranes, namely a lipid self-assembled monolayer and a lipid bilayer tethered to the mercury surface through a hydrophilic spacer (tethered bilayer lipid membrane: tBLM). Incorporation of distinctin into a lipid monolayer from its aqueous solution yields rapidly ion channels selective toward inorganic cations, such as Tl+ and Cd2+. Conversely, its incorporation in a tBLM allows the formation of ion channels permeable to potassium ions only at non-physiological transmembrane potentials, more negative than - 340 mV. These channels, once formed, are unstable at less negative transmembrane potentials. The kinetics of their formation is consistent with the disruption of distinctin clusters adsorbed on top of the lipid bilayer, incorporation of the resulting monomers and their aggregation into hydrophilic pores by a mechanism of nucleation and growth. Comparing the behavior of distinctin in tBLMs with that in conventional black lipid membranes strongly suggests that distinctin channel formation in lipid bilayer requires the partitioning of distinctin molecules between the two sides of the lipid bilayer. We can tentatively hypothesize that an ion channel is formed when one distinctin cluster on one side of the lipid bilayer matches another one on the opposite side.
Original language | English (US) |
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Pages (from-to) | 2745-2752 |
Number of pages | 8 |
Journal | Biochimica et Biophysica Acta - Biomembranes |
Volume | 1808 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2011 |
Bibliographical note
Funding Information:The financial support by Ente Cassa di Risparmio di Firenze (L.B.) , the Italian Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) through PRIN 20079Y9578 (R.G.) and NIH through GM64742 (G.V.) are gratefully acknowledged.
Keywords
- Antimicrobial peptide
- Ion channel
- Lipid monolayer self-assembled on mercury
- Nucleation and growth
- Partially fused vesicle
- Tethered bilayer lipid membrane