Pašalić, Lea; Maleš, Petra; Pem, Barbara; Jakas, Andreja; Wallner, Jakob; Kuvek, Tea; Grundschober, Nadine; Galicia-Andrés, Edgar; Petrov, Dražen; Bakarić, Danijela (2026) Interaction of tryptophan-based peptides with mixed lipid bilayers modulates bilayers’ hydrophobic region in an anionic lipid-dependent manner. Chemistry and Physics of Lipids, 278-79 . ISSN 0009-3084
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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.
| Item Type: | Article | ||||||||
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| Uncontrolled Keywords: | 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG); Cationic hydrophobic peptides R5W2 and K5W2; Spectroscopy (FTIR-ATR and UV-Vis) and calorimetry (DSC); Molecular dynamics (MD) | ||||||||
| Subjects: | NATURAL SCIENCES > Chemistry > Physical Chemistry | ||||||||
| Divisions: | Division of Organic Chemistry and Biochemistry | ||||||||
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| Depositing User: | Danijela Bakarić | ||||||||
| Date Deposited: | 10 Jun 2026 14:57 | ||||||||
| URI: | https://fulir.irb.hr:/id/eprint/12011 | ||||||||
| DOI: | 10.1016/j.chemphyslip.2026.105591 |
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