Regulation of the activity of antimicrobial peptides by the mechanical properties of the host membrane

• Grant number: 18/14215-2
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): September 30, 2018
• Effective date (End): September 29, 2019
• Field of knowledge: Biological Sciences - Biophysics
• Principal Investigator: João Ruggiero Neto
• Grantee: Dayane dos Santos Alvares
• Supervisor abroad: Natalia Wilke
• Home 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
• Local de pesquisa : Universidad Nacional de Córdoba (UNC), Argentina
• Associated to the scholarship: 15/25620-7 - Interaction membrane/peptide: mechanical and electrostatic properties in system with lipid domains, BP.PD

Abstract

Polybia-MP1 (or simply MP1) is a peptide that displays antimicrobial and anticancer activities. We gathered experimental evidences during the doctorate and post-doctorate projects (FAPESP grants #2012/08147-8, #2015/01508-3 and #2015/25620-7) suggesting that (1) a synergy between the anionic lipid phosphatidylserine and liquid ordered domains significantly influences the lytic activity of the membrane-active helical peptide, MP1, and (2) pH appears to regulate the mechanical properties of lipid films in the presence of MP1. Our hypothesis is that changes occurring on the surface of apoptotic or bacterial cell, such as compressibility, elasticity, fluidity modulated by different lipid composition, are key for the selectivity of Polybia-MP1 to these cells. The association of this peptide to membrane affects strongly the structural and dynamics properties of lipids, disturbing the lipid packing. Consequently, much attention has been paid to the effect on the mechanical properties of membranes induced by peptide correlated to the electrostatic and non-electrostatic interactions on its lytic action. Our current focus is, together with Dr. Wilke, to investigate how MP1 affects the mechanical properties of model membranes using SPT (single-particle tracking), FCS (Fluorescence Correlation Spectroscopy) and FRAP (fluorescence recovery after photobleaching) and to correlate to viscoelastic properties through deformation out-of-plane generated with optical tweezers. In these studies, we will use different models for membranes such as Langmuir monolayers (LM), giant unilamellar vesicles (GUVs) and planar lipid bilayers (BLMs). With these studies in mind, it will be possible to provide a better understanding of the action mechanism of MP1 and factors that modulate its action. We expect to get details that connect the mechanical properties of membranes and peptide activity to develop bioactive peptides more effectively.