Kalata B1 and Kalata B2 have a surfactant-like activity in phosphatidylethanolomine-containing lipid membranes

Cranfield, Charles G., Henriques, Sonia Troeira, Martinac, Boris, Duckworth, Paul, Craik, David J. and Cornell, Bruce (2017) Kalata B1 and Kalata B2 have a surfactant-like activity in phosphatidylethanolomine-containing lipid membranes. Langmuir, 33 26: 6630-6637. doi:10.1021/acs.langmuir.7b01642


Author Cranfield, Charles G.
Henriques, Sonia Troeira
Martinac, Boris
Duckworth, Paul
Craik, David J.
Cornell, Bruce
Title Kalata B1 and Kalata B2 have a surfactant-like activity in phosphatidylethanolomine-containing lipid membranes
Journal name Langmuir   Check publisher's open access policy
ISSN 1520-5827
0743-7463
Publication date 2017-07-05
Year available 2017
Sub-type Article (original research)
DOI 10.1021/acs.langmuir.7b01642
Open Access Status Not yet assessed
Volume 33
Issue 26
Start page 6630
End page 6637
Total pages 8
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 2500 Materials Science
3104 Condensed Matter Physics
3110 Surfaces and Interfaces
1607 Spectroscopy
1603 Electrochemistry
Abstract Cyclotides are cyclic disulfide-rich peptides that are chemically and thermally stable and possess pharmaceutical and insecticidal properties. The activities reported for cyclotides correlate with their ability to target phosphatidylethanolamine (PE)-phospholipids and disrupt cell membranes. However, the mechanism by which this disruption occurs remains unclear. In the current study we examine the effect of the prototypic cyclotides, kalata B1 (kB1) and kalata B2 (kB2), on tethered lipid bilayer membranes (tBLMs) using swept frequency electrical impedance spectroscopy. We confirmed that kB1 and kB2 bind to bilayers only if they contain PE-phospholipids. We hypothesize that the increase in membrane conduction and capacitance observed upon addition of kB1 or kB2 is unlikely to result from ion channel like pores but is consistent with the formation of lipidic toroidal pores. This hypothesis is supported by the concentration dependence of effects of kB1 and kB2 being suggestive of a critical micelle concentration event rather than a progressive increase in conduction arising from increased channel insertion. Additionally, conduction behavior is readily reversible when the peptide is rinsed from the bilayer. Our results support a mechanism by which kB1 and kB2 bind to and disrupt PE-containing membranes by decreasing the overall membrane critical packing parameter, as would a surfactant, which then opens or increases the size of existing membrane defects. The cyclotides need not participate directly in the conductive pore but might exert their effect indirectly through altering membrane packing constraints and inducing purely lipidic conductive pores.
Formatted abstract
Cyclotides are cyclic disulfide-rich peptides that are chemically and thermally stable and possess pharmaceutical and insecticidal properties. The activities reported for cyclotides correlate with their ability to target phosphatidylethanolamine (PE)-phospholipids and disrupt cell membranes. However, the mechanism by which this disruption occurs remains unclear. In the current study we examine the effect of the prototypic cyclotides, kalata B1 (kB1) and kalata B2 (kB2), on tethered lipid bilayer membranes (tBLMs) using swept frequency electrical impedance spectroscopy. We confirmed that kB1 and kB2 bind to bilayers only if they contain PE-phospholipids. We hypothesize that the increase in membrane conduction and capacitance observed upon addition of kB1 or kB2 is unlikely to result from ion channel like pores but is consistent with the formation of lipidic toroidal pores. This hypothesis is supported by the concentration dependence of effects of kB1 and kB2 being suggestive of a critical micelle concentration event rather than a progressive increase in conduction arising from increased channel insertion. Additionally, conduction behavior is readily reversible when the peptide is rinsed from the bilayer. Our results support a mechanism by which kB1 and kB2 bind to and disrupt PE-containing membranes by decreasing the overall membrane critical packing parameter, as would a surfactant, which then opens or increases the size of existing membrane defects. The cyclotides need not participate directly in the conductive pore but might exert their effect indirectly through altering membrane packing constraints and inducing purely lipidic conductive pores.
Keyword Chemistry, Multidisciplinary
Chemistry, Physical
Materials Science, Multidisciplinary
Chemistry
Materials Science
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID FT150100398
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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