Title of article :
Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides
Author/Authors :
Ye، نويسنده , , Guofeng and Gupta، نويسنده , , Anju and DeLuca، نويسنده , , Robert and Parang، نويسنده , , Keykavous and Bothun، نويسنده , , Geoffrey D.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
Pages :
6
From page :
76
To page :
81
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.
Keywords :
Peptide , Phase behavior , Domain , lipid bilayer , Permeability , Liposome
Journal title :
Colloids and Surfaces B Biointerfaces
Serial Year :
2010
Journal title :
Colloids and Surfaces B Biointerfaces
Record number :
1971009
Link To Document :
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