Relationship between the photoinduced damage in lipids and membrane permeabilization

Abstract

The generation of reactive species by photosensitization is the principle of photodynamic therapy and also of cutaneous photoaging. Once produced, these species can react with membrane lipids, yielding a large range of photo-oxidized products. These modified lipids alter the properties of the lipid bilayer, changing its organization into domains and leading to increased permeability to some substances. This latter effect has the potential to cause ionic and hydric disbalance in the cell, culminating in cell death. To date, the literature lacks a detailed mechanism of how the chemical changes in the membrane lead to its permeabilization and how this process is affected by the organization in domains. In this project, we will try to answer this question by studying the effect of phenothiazine photosensitizers (methylene blue and DO15) in model membranes (small and giant unilamellar vesicles). For this purpose, we will combine three types of techniques: chemical analysis, especially high performance liquid chromatography coupled to mass spectrometry, to identify and quantify reaction products; phase contrast and fluorescence microscopy, to identify the conditions that lead to loss of membrane integrity and the formation of lipid domains; and molecular dynamics, to test hypotheses and to propose a mechanism of permeabilization of the membrane subjected to photoinduced damage. (AU)