Abstract
Anionic lipid membrane electrostatic potential and solution pH can influence cationic peptide adsorption to these bilayers, especially those containing simultaneously acid and basic residues. Here, we investigate the effects of the pH solution on MP1 (IDWKKLLDAAKQIL-NH2) adsorption to anionic (7POPC:3POPG) lipid vesicles in comparison to its analog H-MP1, with histidines substituting lysines. We used the association of adsorption isotherms and constant pH molecular dynamic simulations (CpHMD) to explore the effects of membrane potential and pH on peptides’ adsorption on this lipid membrane. We analyzed the fluorescence and zeta potential adsorption isotherms using the Gouy–Chapman theory. In CpHMD simulations for the peptides in solution and adsorbed on the lipid bilayer, we used the conformations obtained by conventional MD simulations at a μs timescale. Non-equilibrium Monte Carlo simulations provided the protonation states of acidic and basic residues. CpHMD showed average pKa shifts of two to three units, resulting in a higher net charge for the analog than for MP1, strongly modulating the peptide adsorption. The fractions of the protonation of acidic and basic residues and the peptides’ net charges obtained from the analysis of the adsorption isotherms were in reasonable agreement with those from CpHMD. MP1 adsorption was almost insensitive to solution pH. H-MP1 was much more sensitive to partitioning, at acidic pH, with an affinity ten times higher than in neutral ones.
Highlights
Introduction published maps and institutional affilElectrostatic interactions play a crucial role in the selectivity of the lytic peptides with antimicrobial properties
Peptide Affinity to the Anionic Membrane Investigated by Fluorescence Spectroscopy
We used tryptophan emission fluorescence spectroscopy to investigate the affinity of both peptides to adsorb onto an anionic membrane
Summary
Electrostatic interactions play a crucial role in the selectivity of the lytic peptides with antimicrobial properties. Antimicrobial peptides (AMPs) are rich in cationic and non-polar residues [1,2]. Evidence showed that these peptides act only on the lipidic phase of the plasma membranes without requiring specific membrane receptors. The outer leaflet of microorganism plasma membranes contains considerable amounts of anionic phospholipids [1,3,4,5,6,7,8,9]. The opposition of peptide and membrane charges is the source of their higher selectivity to microorganism membranes. Changing the peptide contents of cationic and non-polar amino acids play an important role in modulating the affinity and lytic activity of different peptides in model membranes [10,11,12]
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