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Disrupting membrane raft domains by alkylphospholipids
A B Gomide1, C H Thomé, G A dos Santos
1Institute of Physics, University of São Paulo, SP, Brazil.
Biochimica Et Biophysica Acta
|February 5, 2013
Summary
Alkylphospholipids like ODPC disrupt simple lipid bilayers but are resisted by sphingomyelin and cholesterol. They rapidly destabilize lipid raft domains, potentially explaining their toxicity to cancer cells.
Area of Science:
- Biophysics
- Cell Biology
- Membrane Biophysics
Background:
- Alkylphospholipids (ALPS) are a class of molecules with potential therapeutic applications.
- Lipid rafts are specialized microdomains within the plasma membrane crucial for cellular signaling.
- Understanding how ALPS interact with lipid bilayers and rafts is key to their application.
Purpose of the Study:
- To investigate the influence of the alkylphospholipid ODPC on giant unilamellar vesicles (GUVs).
- To determine the effect of ODPC on lipid bilayers composed of DOPC, sphingomyelin (SM), and cholesterol (Chol).
- To explore the mechanism of lipid raft disruption by ODPC and its potential correlation with toxicity.
Main Methods:
- Phase contrast and fluorescence microscopy were used to observe GUVs.
- ODPC was added to GUVs with varying lipid compositions (DOPC, SM, Chol).
- Time-lapse imaging tracked membrane disruption, domain dynamics, and GUV rupture.
Main Results:
- ODPC induced disruption of DOPC-only GUVs.
- SM and Chol protected GUVs from ODPC-induced disruption in homogeneous bilayers.
- ODPC rapidly eliminated Lo-Ld phase coexistence domains in DOPC:SM:Chol (1:1:1) GUVs, leading to redistribution and eventual rupture.
- Perifosine exhibited a similar, but more pronounced, effect.
Conclusions:
- ODPC disrupts simple lipid bilayers but is less effective against membranes containing SM and Chol.
- ODPC rapidly disrupts lipid raft-like domains by promoting lipid mixing.
- This initial disruption of lipid rafts by ODPC and perifosine may underlie their toxicity to neoplastic cells by affecting protein localization.
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