Banca de DEFESA: MARIA CECILIA OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : MARIA CECILIA OLIVEIRA
DATA : 15/12/2022
HORA: 10:00
LOCAL: https://conferenciaweb.rnp.br/webconf/rodrigo-194
TÍTULO:

Influence of Phase-Separated Domains on the Permeability of Oxidized Lipid Membranes

PÁGINAS: 183
RESUMO:

Biological membranes are under constant attack of reactive oxygen and nitrogen species (RONS), which may lead to a complex mixture of nitro-oxidized lipids that are responsible for structural and dynamic changes on the membrane. Because of that, nitro-oxidized lipids are also associated with several tumors and inflammatory and neurodegenerative diseases. Moreover, lipid oxidation may induce membrane phase-separated domains, which also drastically affect the membrane function. Evidence suggests that domain interfaces are “hot spots” for pore formation, but the underlying mechanisms remain elusive.There is an urgent need for an improved understanding of oxidation-induced phase separation on membraneproperties. Likewise, the molecular structure at domain interfaces is still needs to be elucidated. To evaluate the effect of lipid nitro-oxidation on the permeability of homogeneous(single-phase)and heterogeneous (phase-separated)phospholipid bilayers (PLBs), we performed atomistic molecular dynamics (MD) simulations using: (1) homogeneous PLBs composed of several isomers ofnitrated and/or oxidized lipids;(2) heterogeneous PLBs composed of coexisting liquid ordered (Lo) and liquid disordered (Ld) domains, where the Ld domainis composed of non-oxidizedand/or oxidized lipids. Our results show that nitrated lipids increase the membrane permeability of homogeneous PLBs by three-fold compared to oxidized lipids. In addition, we show that oxidized lipids in the presence of nitrated lipids decrease the membrane permeability, suggesting a synergistic effect between them. Overall, the permeability of homogeneous and heterogeneous PLBswas comparable, and the presence of oxidized lipids increase the membrane permeability only in homogeneous PLBs. Despite the later, the presence of only 1.5% of lipid aldehydesat the Lo/Ld domain interfaces of heterogeneous PLBs was able to increase the membrane permeability. In consequence of this, we also performed coarse-grained MD simulations to evaluate whether lipid aldehydes have a preference to accumulate at the interface between Lo/Ld domains. Our results show that lipid aldehydes derived from mono-unsaturated lipids accumulate at the interface, but those derived from poly-unsaturated lipids remain in the Ld domain. This study is of interest for photodynamic therapy and plasma medicine for cancer treatment, to understand the effects caused by RONS in cell membranes.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1764199 - RODRIGO MAGHDISSIAN CORDEIRO
Membro Titular - Examinador(a) Interno ao Programa - 1544394 - PAULA HOMEM DE MELLO
Membro Titular - Examinador(a) Externo ao Programa - 1674592 - TIAGO RODRIGUES
Membro Titular - Examinador(a) Externo à Instituição - ANNEMIE BOGAERTS
Membro Titular - Examinador(a) Externo à Instituição - ERIK NEYTS
Membro Suplente - Examinador(a) Interno ao Programa - 312.257.708-90 - YURI ALEXANDRE AOTO - NENHUMA
Membro Suplente - Examinador(a) Externo à Instituição - ANGELA PRIVAT MALDONADO