Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides

Guofeng Ye, Anju Gupta, Robert DeLuca, Keykavous Parang, Geoffrey D. Bothun

Research output: Contribution to journalArticle

Abstract

The effects of a series of low molecular weight water-soluble cationic linear peptide analogs (LPAs, n-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.

Original languageEnglish (US)
Pages (from-to)76-81
Number of pages6
JournalColloids and Surfaces B: Biointerfaces
Volume76
Issue number1
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Liposomes
Peptides
peptides
membranes
Membranes
Transmission Electron Microscopy
Cryogenics
cryogenics
Transmission electron microscopy
Unilamellar Liposomes
transmission electron microscopy
Differential Scanning Calorimetry
low molecular weights
Phase behavior
Hydrophobicity
hydrophobicity
Static Electricity
Hydrophobic and Hydrophilic Interactions
linkages
breast

Keywords

  • Domain
  • Lipid bilayer
  • Liposome
  • Peptide
  • Permeability
  • Phase behavior

ASJC Scopus subject areas

  • Biotechnology
  • Colloid and Surface Chemistry
  • Physical and Theoretical Chemistry
  • Surfaces and Interfaces

Cite this

Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides. / Ye, Guofeng; Gupta, Anju; DeLuca, Robert; Parang, Keykavous; Bothun, Geoffrey D.

In: Colloids and Surfaces B: Biointerfaces, Vol. 76, No. 1, 01.03.2010, p. 76-81.

Research output: Contribution to journalArticle

Ye, Guofeng ; Gupta, Anju ; DeLuca, Robert ; Parang, Keykavous ; Bothun, Geoffrey D. / Bilayer disruption and liposome restructuring by a homologous series of small Arg-rich synthetic peptides. In: Colloids and Surfaces B: Biointerfaces. 2010 ; Vol. 76, No. 1. pp. 76-81.
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