Title
Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides
Document Type
Article
Date of Original Version
3-1-2010
Abstract
The effects of a series of low molecular weight water-soluble cationic linear peptide analogs (LPAs, <1000 MW) with increasing hydrophobic/hydrophilic balance on lipid bilayer phase behavior and permeability were examined using liposomes composed of zwitterionic dipalmitoylphosphatidylcholine (DPPC) and mixed zwitterionic/anionic DPPC/dipalmitoylphosphatidylglycerol (DPPG) lipid bilayers. LPAs were synthesized using a previously reported alkyl linkage strategy as Arg-Cn-Arg-Cn-Lys, where Cn represents the saturated alkyl linkage separating the cationic residues (n = 4, 7, or 11) (Ye et al., 2007 [1]). Differential scanning calorimetry results show that the cationic LPAs bound to and disrupted DPPC and, to a greater extent, DPPC/DPPG phase behavior. When added to preformed unilamellar liposomes, the LPAs led to significant structural changes based on cryogenic transmission electron microscopy (cryo-TEM). Coupling cryo-TEM with carboxyfluorescein leakage studies indicate that the LPAs induced permeabilization through bilayer expansion, which caused membrane thinning. The effects were inconsistent with increasing LPA hydrophobicity, which suggests that a cooperative effect between electrostatic binding and hydrophobic insertion determined the location of LPAs within the bilayer and their membrane activity. Our results for LPA-induced membrane disruption correlate with previous breast cancer cell uptake studies that showed minimal LPA-C4 uptake, but high LPA-C11 uptake through a non-endocytic mechanism. © 2009 Elsevier B.V. All rights reserved.
Publication Title, e.g., Journal
Colloids and Surfaces B: Biointerfaces
Volume
76
Issue
1
Citation/Publisher Attribution
Ye, Guofeng, Anju Gupta, Robert DeLuca, Keykavous Parang, and Geoffrey D. Bothun. "Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides." Colloids and Surfaces B: Biointerfaces 76, 1 (2010): 76-81. doi: 10.1016/j.colsurfb.2009.10.016.