[Seminar] Understanding how short-chain lipids help doxorubicin cross membranes
Manuel Nuno Melo, Faculty of Mathematics and Natural Sciences, Groningen, Netherlands
| When |
18 Jul, 2013
from
11:00 am to 12:00 pm |
|---|---|
| Where | Auditorium |
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Seminar
Title: Understanding how short-chain lipids help doxorubicin cross membranes
Speaker: Manuel Nuno Melo
Affiliation: Molecular Dynamics Group at the Faculty of Mathematics and Natural Sciences, Groningen, Netherlands
Host: João M. Damas and Cláudio M. Soares
Abstract
The (poor) accumulation profile of a chemotherapeutic drug in its target cells is often the limiting factor that dictates that high therapeutic concentrations be used. Recent evidence shows that short-chain lipids, when present in small proportions in a membrane, confer a translocation-enhancing effect to the antitumoral doxorubicin.
The molecular root of this behavior was studied using MD simulations of the drug interacting with membranes with and without the short lipids. Results clearly indicate a decrease in energy of the intermediate state of translocation, as the short lipids now allow the polar moieties of the drug to be solvated deeper into the bilayer core.
Short-chain lipids were also observed to cluster around the drug when a biasing potential was used to keep it at the bilayer center. To test any drug-specific effect the occurrence of spontaneous/transient membrane pores induced by short-chain-lipids was probed by electrophysiology methods, in the presence and absence of drug, to finally arrive at a complete description of the translocation enhancement process.
Manuel Melo graduated in 2005 in Biochemistry, from the Faculty of Sciences of the University of Lisbon. He then pursued his PhD at the same institution, in The Molecular Biophysics group of Prof. Miguel Castanho, studying the interactions of antimicrobial peptides with phospholipid membranes.
In 2010 Manuel earned a Marie Curie postdoctoral fellowship to move to Prof. Siewert-Jan Marrink's Molecular Dynamics group at the Faculty of Mathematics and Natural Sciences of the University if Gronignen. There he has been applying simulation methodologies to elucidate the molecular-level details of drug-membrane interactions.
