Interaction of guanidinium and ammonium cations with phosphatidylcholine and phosphatidylserine lipid bilayers – Calorimetric, spectroscopic and molecular dynamics simulations study

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1865; no. 4; p. 184122
• Main Authors: Pašalić, Lea, Pem, Barbara, Jurašin, Darija Domazet, Vazdar, Mario, Bakarić, Danijela
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2023
• Subjects: 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); 1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (DPPS); Arginine; Calorimetry; Cations; Cell-Penetrating Peptides; Guanidine; Guanidinium (Gdm+) and ammonium (NH4+) cations; Lecithins; Lipid Bilayers - chemistry; Lysine; Molecular dynamics (MD) simulations; Molecular Dynamics Simulation; Phosphatidylserines - chemistry; Spectroscopic (UV–Vis, FTIR) and calorimetric (DSC) study; Spectrum Analysis; 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); Spectroscopic (UV–Vis, FTIR) and calorimetric (DSC) study; 1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (DPPS); Guanidinium (Gdm+) and ammonium (NH4+) cations; Molecular dynamics (MD) simulations; Guanidinium (Gdm(+)) and ammonium (NH(+)) cations
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2023.184122

The ability of arginine-rich peptides to cross the lipid bilayer and enter cytoplasm, unlike their lysine-based analogues, is intensively studied in the context of cell-penetrating peptides. Although the experiments have not yet reconstructed their internalization mechanism, the computational studies have shown that the type or charge of lipid polar groups is one of the crucial factors in their translocation. In order to gain more detailed insight into the interaction of guanidinium (Gdm+) and ammonium (NH4+) cations, as important building blocks in arginine and lysine amino acids, with lipid bilayers, we conducted the experimental and computational study that tackles this phenomenon. The adsorption of Gdm+ and NH4+ on lipid bilayers prepared from a zwitterionic (DPPC) and an anionic (DPPS) lipid was examined by thermoanalytic and spectroscopic techniques. Using temperature-dependent UV–Vis spectroscopy and DSC calorimetry we determined the impact of Gdm+ and NH4+ on the thermotropic properties of lipid bilayers. FTIR data, along with molecular dynamics simulations, unraveled the molecular-level details on the nature of their interactions, showing the proton transfer between NH4+ and DPPS, but not between Gdm+ and DPPS. The findings originated from this work imply that Gdm+ and NH4+ form qualitatively different interactions with lipids of different charge which is reflected in the physico-chemical interactions that arginine-and lysine-based peptides establish at a complex and chemically heterogeneous environment such as the biological membrane. [Display omitted] •Interaction of Gdm+/NH4+/Na+ and DPPC/DPPS bilayers was explored.•Adsorption of Gdm+, unlike NH4+ and Na+, strongly modulates DPPC pretransition.•DPPC bilayers show selectivity towards Gdm+ over NH4+ (and Na+).•FTIR spectra revealed proton transfer between NH4+ and DPPS upon adsorption.