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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

New Insight into the Mechanism of Action of Wasp Mastoparan Peptides: Lytic Activity and Clustering Observed with Giant Vesicles

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Author(s):
dos Santos Cabrera, Marcia P. [1, 2] ; Alvares, Dayane S. [1] ; Leite, Natalia B. [1] ; de Souza, Bibiana Monson [2] ; Palma, Mario S. [2] ; Riske, Karin A. [3] ; Neto, Joao Ruggiero [1]
Total Authors: 7
Affiliation:
[1] UNESP Sao Paulo State Univ, IBILCE, Dept Phys, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] UNESP Sao Paulo State Univ, Ctr Studies Social Insects, Inst Biosci, BR-13506900 Rio Claro, SP - Brazil
[3] UNIFESP Univ Fed Sao Paulo, Dept Biofis, BR-0403932 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Langmuir; v. 27, n. 17, p. 10805-10813, SEP 6 2011.
Web of Science Citations: 34
Abstract

Antimicrobial peptides of the mastoparans family exert their bactericidal activity by binding to lipid membranes, inducing pores or defects and leaking the internal contents of vesicles and cells. However, this does not seem to be the only mechanism at play, and they might be important in the search for improved peptides with lower undesirable side effects. This work deals with three mastoparans peptides, Polybia-MP-1(MP-1), N2-Polybia-MP-1 (N-MP-1), and Mastoparan X (MPX), which exhibit high sequence homology. They all have three lysine residues and amidated C termini, but because of the presence of two, one, and no aspartic acid residues, respectively, they have +2, +3, and +4 net charges at physiological pH. Here we focus on the effects of these mastoparans peptides on anionic model membranes made of palmitoleyoilphosphatidylcholine (POPC) and palmitoleyoilphosphatidylglycerol (POPG) at 1:1 and 3:1 molar ratios in the presence and in the absence of saline buffer. Zeta potential experiments were carried out to measure the extent of the peptides' binding and accumulation at the vesicle surface, and CD spectra were acquired to quantify the helical structuring of the peptides upon binding. Giant unilamellar vesicles were observed under phase contrast and fluorescence microscopy. We found that the three peptides induced the leakage of GUVs at a gradual rate with many characteristics of the graded mode. This process was faster in the absence of saline buffer. Additionally, we observed that the peptides induced the formation of dense regions of phospholipids and peptides on the GUV surface. This phenomenon was easily observable for the more charged peptides.(MPX > N-MP-1 > MP-1) and in the absence of added salt. Our data suggest that these mastoparans accumulate on the bilayer surface and induce a transient interruption to its barrier properties, leaking the vesicle contents. Next, the bilayer recovers its continuity, but this happens in an inhomogeneous way, forming a kind of ply with peptides sandwiched between two juxtaposed membranes. Eventually, a peptide-lipid aggregate forming a lump is formed at high peptide-to-lipid ratios. (AU)

FAPESP's process: 06/57122-7 - Searching for lead compounds for rational development of new drugs and pesticides through bioprospecting in Brazilian arthropods
Grantee:Mario Sergio Palma
Support type: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 10/11823-0 - Mechanisms of interactions of lipid bilayers and amphiphilic substances of therapeutic interest
Grantee:Marcia Perez dos Santos Cabrera
Support type: Scholarships in Brazil - Post-Doctorate