Defining raft domains in the plasma membrane

Area of Science:

• Cell Biology
• Biophysics
• Biochemistry

Background:

• Plasma membrane (PM) functions are critically dependent on cholesterol concentration.
• Cholesterol's role is nonlinear, with full functionality at physiological levels (35-45 mol%) and loss of function below 25 mol%.

Purpose of the Study:

• To review and define cholesterol-based raft domains in the plasma membrane.
• To propose a working definition for raft domains based on cooperative molecular interactions.

Main Methods:

• Examination of results from fluorescent lipid analogs.
• Analysis of literature on liquid-ordered (Lo)-phase domains, Lo-phase-like domains, and detergent-resistant membranes.
• Logical establishment of fluorescent lipid probes for raft and non-raft domains.

Main Results:

• Identified fundamental similarities between Lo-phase domains, Lo-phase-like domains, and detergent-resistant membranes.
• Demonstrated that these domains form via cooperative interactions of cholesterol, saturated, and unsaturated acyl chains (>25 mol% cholesterol).
• Provided evidence for the existence and essential roles of these domains in PM signal transduction.

Conclusions:

• Raft domains are liquid-like molecular complexes formed by cooperative interactions involving cholesterol, saturated, and unsaturated acyl chains.
• These domains facilitate molecular movement and exchange within the bulk PM.
• A defined set of fluorescent lipid probes can distinguish between raft and non-raft domains in the PM.