Modified LDLs induce and bind to membrane ruffles on macrophages.

Area of Science:

• Cell Biology
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Macrophage foam cell formation is crucial in atherosclerosis.
• Modified low-density lipoproteins (LDL) are key in this process.
• Specific modified LDLs, including acetylated LDL (AcLDL), oxidized LDL (OxLDL), and beta-migrating very low density lipoprotein (betaVLDL), are implicated.

Purpose of the Study:

• To investigate the dynamic cellular responses of macrophages to different modified LDLs.
• To examine the ultrastructure and binding characteristics of AcLDL-induced membrane structures.
• To differentiate the effects of AcLDL, OxLDL, and betaVLDL on macrophage plasma membrane morphology.

Main Methods:

• Time-lapse Allen video enhanced contrast differential interference contrast (AVEC-DIC) light microscopy.
• Correlative whole mount intermediate-voltage transmission electron microscopy (IVEM).
• Stereo 3D surface replica analysis to confirm ligand binding.

Main Results:

• AcLDL and OxLDL significantly stimulated membrane ruffle formation in macrophages.
• betaVLDL primarily increased the number of microvilli on the macrophage surface.
• AcLDL was observed to bind specifically to the induced membrane ruffles, confirmed by 3D surface replicas.
• Quantification revealed AcLDL promotes ruffling, while betaVLDL and LDL promote microvilli formation.

Conclusions:

• Modified LDLs induce distinct changes in macrophage plasma membrane morphology.
• AcLDL specifically induces and binds to circular membrane ruffles.
• These findings provide insights into the cellular mechanisms of modified LDL uptake and foam cell formation.