Effect of Membrane Potential on the Adsorption of pH-Responsive Bioactive Peptides on Anionic Lipid Membranes

• Grant number: 24/10235-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Dayane dos Santos Alvares
• Grantee: Thiago de Lucca Almeida Lima
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated research grant: 22/07231-7 - Plasticity and functional modulation of intrinsically disordered proteins, AP.TEM

Abstract

This project aims to investigate the effect of membrane potential on the adsorption of pH-responsive peptides on anionic lipid membranes, focusing on the substitution of lysines with histidines. The substitution of lysine residues with histidine is particularly relevant because histidines have a pKa close to the physiological range, making the peptide charge sensitive to small pH variations. This study aims to understand how the modulation of peptide charge, due to the exchange of lysine for histidine, influences the interaction of these peptides with model membranes, with significant implications for the development of anti-tumor drugs. To achieve this, analogs of the original peptides will be synthesized, where lysines will be gradually replaced by histidines. The planned substitution will allow us to observe how different degrees of substitution affect the affinity and activity of the peptides under various pH conditions. We will use biophysical techniques, such as fluorescence spectroscopy and zeta potential measurements, to evaluate the electrostatic interaction between the modified peptides and lipid membranes. Additionally, the Gouy-Chapman theory will be applied to analyze the adsorption isotherms of the peptides on the membranes. Applying this theory will enable us to quantify how the peptide charge, influenced by the substitution of lysines with histidines and by the environmental pH, modulates their adsorption on lipid membranes. This will help us better understand the electrostatic contributions to the affinity of peptides for anionic membranes.