Membrane restructuring via ceramide results in enhanced solute efflux
L Ruth Montes1, M Begoña Ruiz-Argüello, Félix M Goñi
1Unidad de Biofisica (Centro Mixto Consejo Superior de Investigaciones Cientificas/Universidad del Pais Vasco/Euskal Herriko Unibertsitatea) Bilbao, Spain.
The Journal of Biological Chemistry
|January 18, 2002
Summary
Ceramides can alter cell membrane permeability, causing vesicle content release. Enzymatically generated ceramides induce faster and greater membrane efflux than added ceramides, suggesting a role in membrane restructuring.
Area of Science:
- Biochemistry
- Membrane Biology
- Cell Biology
Background:
- Ceramides are key signaling lipids involved in various cellular processes.
- The precise mechanisms by which ceramides affect membrane permeability are not fully understood.
- Understanding ceramide's role in membrane dynamics is crucial for deciphering cellular signaling and disease pathogenesis.
Purpose of the Study:
- To investigate the capacity of ceramides to modify cell membrane permeability.
- To compare the effects of in situ generated ceramides versus externally added ceramides on membrane efflux.
- To elucidate the biophysical properties of ceramides contributing to membrane restructuring.
Main Methods:
- Utilized large unilamellar vesicles (LUVs) composed of phospholipids and cholesterol.
- Incorporated fluorescent molecules within vesicles to quantify ceramide-dependent efflux.
- Generated ceramides enzymatically (sphingomyelinase) or added them exogenously.
- Investigated the effect of N-acetylsphingosine (C(2)-ceramide) and long-chain ceramides.
Main Results:
- Long-chain ceramides, whether added or enzymatically produced, induced release of vesicle contents.
- Enzymatically generated ceramides caused faster and more extensive efflux compared to externally added ceramides.
- N-acetylsphingosine (C(2)-ceramide) at 10 mol% did not induce significant efflux.
- Sphingomyelinase treatment of bilayers with 50 mol% sphingomyelin released large molecules (dextrans > 20 kDa).
- Ceramide's ability to induce negative monolayer curvature and form ceramide-rich domains are key to membrane restructuring.
Conclusions:
- Ceramides significantly impact cell membrane permeability and induce content efflux.
- The method of ceramide generation influences the extent and rate of membrane permeabilization.
- Ceramide-induced membrane restructuring involves specific biophysical properties like negative curvature induction and domain formation.
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