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Relationship between the photoinduced damage in lipids and membrane permeabilization

Grant number: 13/11640-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2013
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Mauricio da Silva Baptista
Grantee:Isabel de Oliveira Lima Bacellar
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/50680-5 - Photosensitization in life sciences, AP.TEM
Associated scholarship(s):15/22935-7 - Study of photosensitized radical-mediated lipid oxidation by the use of a BODIPY-a-tocopherol off/on fluorescent probe in model membranes, BE.EP.DD


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)

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BACELLAR, ISABEL O. L.; CORDEIRO, RODRIGO M.; MAHLING, PASCAL; BAPTISTA, MAURICIO S.; ROEDER, BEATE; HACKBARTH, STEFFEN. Oxygen distribution in the fluid/gel phases of lipid membranes. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1861, n. 4, p. 879-886, APR 1 2019. Web of Science Citations: 1.
BACELLAR, ISABEL O. L.; BAPTISTA, MAURICIO S.; JUNQUEIRA, HELENA C.; WAINWRIGHT, MARK; THALMANN, FABRICE; MARQUES, CARLOS M.; SCHRODER, ANDRE P. Permeability of DOPC bilayers under photoinduced oxidation: Sensitivity to photosensitizer. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1860, n. 11, p. 2366-2373, NOV 2018. Web of Science Citations: 2.
BACELLAR, ISABEL O. L.; OLIYEIRA, MARIA CECILIA; DANTAS, LUCAS S.; COSTA, ELIERGE B.; JUNQUEIRA, HELENA C.; MARTINS, WALESKA K.; DURANTINI, ANDRES M.; COSA, GONZALO; DI MASCIO, PAOLO; WAINWRIGHT, MARK; MIOTTO, RONEI; CORDEIRO, RODRIGO M.; MIYAMOTO, SAYURI; BAPTISTA, MAURICIO S. Photosensitized Membrane Permeabilization Requires Contact-Dependent Reactions between Photosensitizer and Lipids. Journal of the American Chemical Society, v. 140, n. 30, p. 9606-9615, AUG 1 2018. Web of Science Citations: 16.
BACELLAR, ISABEL O. L.; TSUBONE, TAYANA M.; PAVANI, CHRISTIANE; BAPTISTA, MAURICIO S. Photodynamic Efficiency: From Molecular Photochemistry to Cell Death. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 16, n. 9, p. 20523-20559, SEP 2015. Web of Science Citations: 94.

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