title: Self-assembly and interactions of short antimicrobial cationic lipopeptides with membrane lipids: ITC, FTIR and molecular dynamics studies.
abstract: In this work, the self-organization and the behavior of the surfactant-like peptides in the presence of biological membrane models were studied. The studies were focused on synthetic palmitic acid-containing lipopeptides, C16-KK-NH2 (I), C16-KGK-NH2 (II) and C16-KKKK-NH2 (III). The self-assembly was explored by molecular dynamics simulations using a coarse-grained force field. The critical micellar concentration was estimated by the surface tension measurements. The thermodynamics of the peptides binding to the anionic and zwitterionic lipids were established using isothermal titration calorimetry (ITC). The influence of the peptides on the lipid acyl chain ordering was determined using FTIR spectroscopy. The compounds studied show surface-active properties with a distinct CMC over the millimolar range. An increase in the steric and electrostatic repulsion between polar head groups shifts the CMC toward higher values and reduces the aggregation number. An analysis of the peptide-membrane binding revealed a unique interplay between the initial electrostatic and the subsequent hydrophobic interactions enabling the lipopeptides to interact with the lipid bilayer. In the case of C16-KKKK-NH2 (III), compensation of the electrostatic and hydrophobic interactions upon binding to the anionic membrane has been suggested and consequently no overall binding effects were noticed in ITC thermograms and FTIR spectra.
authors: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland. Electronic address: emilia.sikorska@ug.edu.pl.
authors: Emilia
authors: E
authors: Sikorska
authors: Faculty of Pharmacy with Subfaculty of Laboratory Medicine, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors: Małgorzata
authors: M
authors: Dawgul
authors: Faculty of Pharmacy with Subfaculty of Laboratory Medicine, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors: Katarzyna
authors: K
authors: Greber
authors: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
authors: Emilia
authors: E
authors: Iłowska
authors: Faculty of Pharmacy with Subfaculty of Laboratory Medicine, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors: Aneta
authors: A
authors: Pogorzelska
authors: Faculty of Pharmacy with Subfaculty of Laboratory Medicine, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors: Wojciech
authors: W
authors: Kamysz
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002151:Calorimetry; D057927:Hydrophobic and Hydrophilic Interactions; D055666:Lipopeptides / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D019308:Palmitic Acid / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: D023181:Antimicrobial Cationic Peptides; D055666:Lipopeptides; D008563:Membrane Lipids; D019308:Palmitic Acid
keywords: Coarse-grained molecular dynamics; FTIR; ITC; Lipopeptide; Self-assembling process; Surfactant-like peptide