Modulatory Effects of Acidic pH and Membrane Potential on the Adsorption of pH-Sensitive Peptides to Anionic Lipid Membrane

Author(s)

Alvares, Dayane dos Santos ; Martins, Ingrid Bernardes Santana ; Viegas, Taisa Giordano ; Palma, Mario Sergio ; de Araujo, Alexandre Suman ; de Carvalho, Sidney Jurado ; Ruggiero Neto, Joao

• Document type: Journal article
• Source: MEMBRANES; v. 11, n. 5, p. 16-pg., 2021-05-01.

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 mu s 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. (AU)

• FAPESP's process: 15/25620-7 - Interaction membrane/peptide: mechanical and electrostatic properties in system with lipid domains
• Grantee: Dayane dos Santos Alvares
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/18169-3 - Investigations of physical chemistry processes related with the binding of environmental relevant heavy metal ions by calix[4]arenes using molecular dynamics simulations
• Grantee: Alexandre Suman de Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/16212-5 - Natural proteopeptides from the Brazilian fauna, flora and microbiota as potential models for the rational development of new drugs of therapeutic use: isolation, structure elucidation, chemical synthesis and functional activity assays
• Grantee: Mario Sergio Palma
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 18/01841-2 - Computational Simulation Studies on the Interaction Between Polyelectrolytes and Macromolecules
• Grantee: Sidney Jurado de Carvalho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/25619-9 - Effect of aminophospholipids and of the pH on the interfacial activity of the anticancer peptide Polybia-MP1 and analogs in model membranes
• Grantee: João Ruggiero Neto
• Support Opportunities: Regular Research Grants