Human LDL core cholesterol ester packing: three-dimensional image reconstruction and SAXS simulation studies

Area of Science:

• Biophysics
• Structural Biology
• Lipid Metabolism

Background:

• Human low-density lipoprotein (LDL) exhibits a reversible thermal phase transition.
• This transition is linked to cholesterol ester packing within the LDL lipid core.
• Prior studies suggest structural changes impact LDL's oxidative resistance.

Purpose of the Study:

• To investigate the three-dimensional (3D) structural and morphological changes in human LDL following its thermal phase transition.
• To elucidate the alterations in lipid packing within the LDL core after the order-disorder transition.

Main Methods:

• Cryo-preservation of human LDL at 53°C (above the phase transition temperature).
• Examination using electron microscopy and 3D image reconstruction.
• Simulation of small-angle X-ray scattering (SAXS) curves and comparison with existing data.

Main Results:

• LDL particles cryo-preserved above the phase transition displayed altered morphology.
• The central lipid core density layer was disrupted.
• A "disrupted shell" density was observed beneath the surface layer, indicating an intermediate lipid packing state.

Conclusions:

• The study provides 3D visualization of lipid packing during the LDL lipid-core phase transition.
• The observed "disrupted shell" structure represents a transitional state between isotropic and layered lipid packing.
• These findings enhance understanding of LDL structural dynamics and its lipid core organization.