The lipids C2- and C16-ceramide form large stable channels. Implications for apoptosis

Area of Science:

• Biochemistry
• Cell Biology
• Membrane Biophysics

Background:

• Ceramides are lipids involved in various cellular processes.
• The membrane-forming capabilities of ceramides at physiological concentrations are not fully understood.
• Understanding ceramide's role in membrane permeability is crucial for cell signaling and apoptosis.

Purpose of the Study:

• To investigate the pore-forming activity of ceramides in biological membranes.
• To explore the structural basis and functional consequences of ceramide-induced pores.
• To assess the role of dihydroceramide in comparison to ceramide.

Main Methods:

• * Investigated ceramide and dihydroceramide activity in membranes at physiological concentrations.
• * Utilized structural modeling to elucidate pore formation mechanisms.
• * Employed mathematical modeling to correlate ceramide concentration with membrane conductance.
• * Assessed the permeability of pores to molecules like cytochrome c.

Main Results:

• * Both short- and long-chain ceramides form large, stable pores in membranes at physiological concentrations.
• * These ceramide pores are sufficiently large to permit cytochrome c passage.
• * Dihydroceramide exhibits markedly reduced apoptogenic and channel-forming activities compared to ceramide.
• * Mathematical models show a direct relationship between ceramide concentration and both individual channel and overall membrane conductance.
• * Small changes in ceramide concentration lead to significant alterations in pore size and membrane permeability.

Conclusions:

• Ceramides, at physiological levels, act as pore-forming agents in membranes, influencing membrane permeability.
• The structural and concentration-dependent properties of ceramide pores suggest a regulatory mechanism for membrane function.
• Ceramide-mediated pore formation may play a significant role in the process of apoptosis.