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Updated: Jun 1, 2026

Measuring Peptide Translocation into Large Unilamellar Vesicles
Published on: January 27, 2012
Interaction of tryptophan-based peptides with mixed lipid bilayers modulates bilayers' hydrophobic region in an
Lea Pašalić1, Petra Maleš1, Barbara Pem2
1Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, Zagreb 10000, Croatia.
Abstract:
The transport of substances between the cell and its environment is influenced by lipid redistribution within and between membrane leaflets. The mechanism of cell-penetrating peptides (CPPs) passing through membranes depends on the peptide's characteristics and the lipid composition. This study examined interactions between mixed lipid membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and varying anionic lipids (1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) or 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS)), along with CPPs that share a hydrophobic group (tryptophan (W)) and a variable positively charged group (arginine (R) or lysine (K)). Results showed that the presence of peptides significantly affected the thermotropic properties of the DPPC + DPPS mixture more than the DPPC + DPPG mixture, with changes depending on the cationic amino acid. FTIR spectra and MD simulations indicated that peptide penetration depth is more influenced by anionic lipids than the lipid phase. Importantly, interactions with DPPG or DPPS lipids caused qualitatively different alterations in the bilayer's non-polar region, with R5W2 displaying greater insertion capacity than K5W2. These findings suggest that the interactions between CPPs and the lipid bilayer's polar groups have broader effects on the entire membrane structure.
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