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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
77
11-POS
Board 6
Modulation of the Membrane Properties by an Ether-Lipid Derivate and Its Consequences
in Metastasis Development
Ana Bouchet
1,5
, Fernando Herrera
2
, Charlotte Sevrain
3,5
, Hèlène Couthon-Gourvès
3,5
, Paul-
Alain Jaffrès
3,5
, Aurélie Chantôme
1,5
, Marie Potier-Cartereau
1,5
, Jose Requejo-Isidro
4
, Christophe
Vandier
1,5
.
1
Université François Rabelais de Tours, Tours, France,
2
Universidad Nacional del Litoral, Santa
Fe, Argentina,
3
Université de Brest, Brest, France,
5
Network and cancer-Canceropole Grand
Ouest, Tours, France.
4
Unidad de Biofisica (CSIC-UPV/EHU), Leioa, Spain,
Specific properties of lipid organisation (fluidity, phase separation, thickness) regulate the
structure and activity of membrane proteins, including ion channels. Their role in the regulation
of several diseases has been pointed out during the last decade. Our previous data have shown
that the SK3 channel (a calcium-activated potassium channel) is involved in the migration of
various cancer cells (1). Interestingly an ether-lipid derivate named Ohmline modulates the
activity of this channel. The decrease in channel activity by Ohmline is associated with a
reduction of cancer cell migrations but does not affect the migration of non-cancer cells (2).
Many antecedents indicate that during cell migration a change in membrane fluidity occurs in the
plasma membrane of cancer cells providing evidence of a pivotal role of biophysical adaptation
in this biological process that ultimately lead to metastatic development.
In the present work, we characterise the physicochemical properties of Ohmline in various lipid
environments. Molecular dynamic simulations suggest that Ohmline molecules organize
differently depending on the lipid bilayer nature. Fluorescence spectroscopy on model lipid
membranes confirm that Ohmline modulates the bilayer order. Imaging the lipid-packing state
upon treatment of live cells with Ohmline supports the model in-situ.
The consequences of these observations will be discussed in terms of therapeutic prospectives in
tumour development and more particularly in metastasis development.
References:
(1) Girault A, et al. (2012) Curr. Med. Chem., 19, 697-713
(2) Girault A, et al. (2011) Current Cancer Drug Target, 11, 1111-1125