Antimicrobial Peptide K-0-W-6-Hya1 Induces Stable Structurally Modified Lipid Domains in Anionic Membranes

Author(s)

Enoki, Thais A. ^{[1, 2]} ; Moreira-Silva, Isabela ^[3] ; Lorenzon, Esteban N. ^[4] ; Cilli, Eduardo M. ^[5] ; Perez, Katia R. ^[3] ; Riske, Karin A. ^[3] ; Teresa Lamy, M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Fis, BR-05508090 Sao Paulo, SP - Brazil

^[2] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14850 - USA

^[3] Univ Fed Sao Paulo, Dept Biofis, BR-04039032 Sao Paulo, SP - Brazil

^[4] Univ Fed Goias, Inst Ciencias Biol, Dept Bioquim & Biol Mol, BR-74690900 Goiania, Go - Brazil

^[5] Univ Estadual Sao Paulo, Inst Quim, BR-14800060 Araraquara, SP - Brazil

• Document type: Journal article
• Source: Langmuir; v. 34, n. 5, p. 2014-2025, FEB 6 2018.
• Web of Science Citations: 6

Abstract

Considering the known different mode of action of antimicrobial peptides in zwitterionic and anionic cell membranes, the present work compares the action of the antimicrobial peptide K-0-W-6-Hya1 (KIFGAIWPLALGALICNLIK-NH2) with zwitterionic and negatively charged model membranes, namely, liposomes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) membranes, and a mixture of the two. Differential scanning calorimetry (DSC), steady state fluorescence of the Trp residue, dynamic light scattering (DLS), and measurement of the leakage of an entrapped fluorescent dye (carboxyfluorescein, CF) were performed with large unilamellar vesicles (LUVs). All techniques evidenced the different action of the peptide in zwitterionic and anionic vesicles. Trp fluorescence spectroscopy shows that the differences are related not only to the partition of the cationic peptide in zwitterionic and anionic membranes, but also to the different penetration depth of the peptide into the lipid bilayers: Trp goes deeper into negatively charged membranes, both in the gel and fluid phases, than into zwitterionic ones. DSC shows that the peptide is strongly attached to anionic bilayers, giving rise to the coexistence of two different lipid regions, one depleted of peptide and another one peptide-disturbed, possibly a stable or transient polar pore, considering the leakage of CF. This contrasts with the homogeneous effect produced by the peptide in zwitterionic membranes, probably related to peptide-membrane diffusion. Moreover, in mixed bilayers (PC:PG), the peptide sequesters negatively charged lipids, creating peptide-rich anionic lipid regions, strongly disturbing the membrane. The distinct structural interaction displayed by the peptide in PC and PG membranes could be related to the different mechanisms of action of the peptide in anionic prokaryotic and zwitterionic eukaryotic cell membranes. (AU)

• FAPESP's process: 13/14419-3 - Aqueous dispersions of biologically relevant amphiphilic aggregates: structures and interactions studies
• Grantee: Maria Teresa Moura Lamy
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/11671-5 - Interaction of antimicrobial peptides with model membranes.
• Grantee: Thais Azevedo Enoki Liarte
• Support Opportunities: Scholarships in Brazil - Doctorate