Smaller discoidal high-density lipoprotein particles form saddle surfaces, but not planar bilayers

Area of Science:

• Biochemistry
• Lipidomics
• Structural Biology

Background:

• Discoidal high-density lipoprotein (HDL) particles exist in various sizes in plasma.
• Structural differences and size-regulating factors of HDL particles are not fully understood.
• HDL particle behavior varies significantly with size.

Purpose of the Study:

• To investigate the structural differences between reconstituted HDL (rHDL) particles of varying sizes.
• To identify factors regulating the size of HDL particles.
• To elucidate the relationship between rHDL size, lipid composition, and surface properties.

Main Methods:

• Preparation of reconstituted HDLs (rHDLs) with varying phospholipid (PL) to apolipoprotein A-I (apoA-I) ratios.
• Structural evaluation using gel filtration chromatography.
• Fluorometric analyses to assess lipid bilayer properties (lateral pressure and hydration) using dipyrenylphosphatidylcholine and dansyl phosphatidylethanolamine.

Main Results:

• Unsaturated PLs formed rHDLs of 9.5-9.6 nm, 8.8-9.0 nm, and 7.8-7.9 nm diameters.
• Saturated PLs exclusively formed the largest rHDLs (9.5-9.9 nm).
• Smaller rHDLs exhibited reduced cholesterol content, lower lateral pressure, and decreased surface hydration compared to larger rHDLs, adopting a saddle surface structure.

Conclusions:

• HDL particle size is regulated by phospholipid saturation and initial PL:apoA-I ratios.
• Smaller rHDLs possess distinct structural and surface properties (saddle surface, lower cholesterol, reduced hydration) compared to larger, planar bilayer rHDLs.
• These findings provide insights into the structural diversity and formation mechanisms of HDL particles.