期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 76, 期 1, 页码 76-81出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2009.10.016
关键词
Peptide; Lipid bilayer; Liposome; Phase behavior; Domain; Permeability
资金
- American Cancer Society [RSG-07-290-01-CDD]
- National Science Foundation [CHE 0748555]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [748555] Funding Source: National Science Foundation
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-C-n-Arg-C-n-Lys, where C-n 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-C-4 uptake, but high LPA-C-11 uptake through a non-endocytic mechanism. (C) 2009 Elsevier B.V. All rights reserved.
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