Lipid Membrane Interactions of the Cationic Antimicrobial Peptide Chimeras Melimine and Cys-Melimine

Berry, T; Dutta, D; Chen, R; Leong, A; Wang, H; Donald, WA; Parviz, M; Cornell, B; Willcox, M; Kumar, N; Cranfield, CG

Lipid Membrane Interactions of the Cationic Antimicrobial Peptide Chimeras Melimine and Cys-Melimine

Berry, T

Dutta, D Chen, R Leong, A Wang, H Donald, WA Parviz, M

Cornell, B

Willcox, M Kumar, N Cranfield, CG

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Publication Type:: Journal Article
Citation:: Langmuir, 2018, 34 (38), pp. 11586 - 11592
Issue Date:: 2018-09-25

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Field	Value	Language
dc.contributor.author	Berry, T https://orcid.org/0000-0002-2882-0313	en_US
dc.contributor.author	Dutta, D	en_US
dc.contributor.author	Chen, R	en_US
dc.contributor.author	Leong, A	en_US
dc.contributor.author	Wang, H	en_US
dc.contributor.author	Donald, WA	en_US
dc.contributor.author	Parviz, M https://orcid.org/0000-0002-0696-9205	en_US
dc.contributor.author	Cornell, B https://orcid.org/0000-0003-4166-3241	en_US
dc.contributor.author	Willcox, M	en_US
dc.contributor.author	Kumar, N	en_US
dc.contributor.author	Cranfield, CG https://orcid.org/0000-0003-3608-5440	en_US
dc.date.issued	2018-09-25	en_US
dc.identifier.citation	Langmuir, 2018, 34 (38), pp. 11586 - 11592	en_US
dc.identifier.issn	0743-7463	en_US
dc.identifier.uri	http://hdl.handle.net/10453/130644
dc.description.abstract	Copyright © 2018 American Chemical Society. Melimine and its derivatives are synthetic chimeric antimicrobial agents based on protamine and melittin. The binding of solubilized melimine and its derivative, with a cysteine on N-terminus, (cys-melimine) on tethered bilayer lipid membranes (tBLMs) was examined using ac electrical impedance spectroscopy. The addition of melimine and cys-melimine initially increased membrane conduction, which subsequently falls over time. The results were obtained for tBLMs comprising zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, or tBLMs made using purified lipids from Escherichia coli. The effect on conduction is more marked with the cysteine variant than the noncysteine variant. The variation in membrane conduction most probably arises from individual melimines inducing increased ionic permeability, which is then reduced as the melimines aggregate and phase-separate within the membrane. The actions of these antimicrobials are modeled in terms of altering the critical packing parameter (CPP) of the membranes. The variations in the peptide length of cys-melimine were compared with a truncated version of the peptide, cys-mel4. The results suggest that the smaller molecule impacts the membrane by a mechanism that increases the average CPP, reducing membrane conduction. Alternatively, an uncharged alanine-replacement version of melimine still produced an increase in membrane conduction, further supporting the CPP model of geometry-induced toroidal pore alterations. All the data were then compared to their antimicrobial effectiveness for the Gram-positive and Gram-negative strains of bacteria, and their fusogenic properties were examined using dynamic light scattering in 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine lipid spheroids. We conclude that a degree of correlation exists between the antimicrobial effectiveness of the peptides studied here and their modulation of membrane conductivity.	en_US
dc.relation	http://purl.org/au-research/grants/arc/DP160101664
dc.relation.ispartof	Langmuir	en_US
dc.relation.isbasedon	10.1021/acs.langmuir.8b01701	en_US
dc.subject.classification	Chemical Physics	en_US
dc.subject.mesh	Pseudomonas aeruginosa	en_US
dc.subject.mesh	Escherichia coli	en_US
dc.subject.mesh	Staphylococcus aureus	en_US
dc.subject.mesh	Staphylococcus epidermidis	en_US
dc.subject.mesh	Cysteine	en_US
dc.subject.mesh	Lipid Bilayers	en_US
dc.subject.mesh	Antimicrobial Cationic Peptides	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Microbial Sensitivity Tests	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Permeability	en_US
dc.title	Lipid Membrane Interactions of the Cationic Antimicrobial Peptide Chimeras Melimine and Cys-Melimine	en_US
dc.type	Journal Article
utslib.citation.volume	38	en_US
utslib.citation.volume	34	en_US
utslib.for	0303 Macromolecular and Materials Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	closed_access
pubs.issue	38	en_US
pubs.publication-status	Published	en_US
pubs.volume	34	en_US

Abstract:

Copyright © 2018 American Chemical Society. Melimine and its derivatives are synthetic chimeric antimicrobial agents based on protamine and melittin. The binding of solubilized melimine and its derivative, with a cysteine on N-terminus, (cys-melimine) on tethered bilayer lipid membranes (tBLMs) was examined using ac electrical impedance spectroscopy. The addition of melimine and cys-melimine initially increased membrane conduction, which subsequently falls over time. The results were obtained for tBLMs comprising zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, or tBLMs made using purified lipids from Escherichia coli. The effect on conduction is more marked with the cysteine variant than the noncysteine variant. The variation in membrane conduction most probably arises from individual melimines inducing increased ionic permeability, which is then reduced as the melimines aggregate and phase-separate within the membrane. The actions of these antimicrobials are modeled in terms of altering the critical packing parameter (CPP) of the membranes. The variations in the peptide length of cys-melimine were compared with a truncated version of the peptide, cys-mel4. The results suggest that the smaller molecule impacts the membrane by a mechanism that increases the average CPP, reducing membrane conduction. Alternatively, an uncharged alanine-replacement version of melimine still produced an increase in membrane conduction, further supporting the CPP model of geometry-induced toroidal pore alterations. All the data were then compared to their antimicrobial effectiveness for the Gram-positive and Gram-negative strains of bacteria, and their fusogenic properties were examined using dynamic light scattering in 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine lipid spheroids. We conclude that a degree of correlation exists between the antimicrobial effectiveness of the peptides studied here and their modulation of membrane conductivity.

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http://hdl.handle.net/10453/130644