Single-aggregate morphological and biomechanical detection of atherogenic aggregated low-density lipoprotein (agLDL) by atomic force microscopy

Area of Science:

• Cardiovascular Biology
• Biophysics
• Biochemistry

Background:

• Aggregated low-density lipoprotein (agLDL) is implicated in atherosclerosis, but its mechanisms remain unclear.
• Understanding agLDL's atherogenicity is crucial for developing effective prevention strategies.

Purpose of the Study:

• To investigate the mechanisms behind agLDL's atherogenicity.
• To characterize the morphological and biomechanical properties of agLDL.

Main Methods:

• agLDL was induced using physical (vortexing) or biological (alpha-chymotrypsin, sphingomyelinase) methods.
• Aggregation was verified using turbidimetry and size distribution analysis.
• Atomic force microscopy (AFM) was used to assess single-aggregate properties.

Main Results:

• agLDL exhibited aggregation degree-dependent atherogenic properties.
• agLDL particles were found to be softer (lower Young's modulus) and stickier (higher adhesion force) than native LDL.
• Intra-aggregate LDL within agLDL showed a larger average size compared to native LDL monomers.

Conclusions:

• The altered biomechanical properties (softer, stickier) of agLDL likely contribute to its atherogenicity.
• Targeting the biomechanical characteristics of agLDL may offer a novel therapeutic approach for atherosclerosis prevention.