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 ). 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.
- Lipid bilayer
- Phase behavior
ASJC Scopus subject areas
- Colloid and Surface Chemistry
- Physical and Theoretical Chemistry
- Surfaces and Interfaces