Heterogeneity of low-density lipoprotein in chicken egg yolk

Low-density lipoprotein (LDL) from chicken egg yolk is a natural nanoemulsion with a broad particle size distribution and pronounced heterogeneity. In this study, LDL was fractionated into five size fractions, whose structural and compositional properties were systematically compared. As particle size decreased (72 nm to 33 nm), LDL morphology changed from large, irregular aggregates to compact, spherical particles with clear boundaries and a more uniform size distribution, reflecting differences in aggregation state and structural stability. Spectroscopic analyses showed that the protein moieties of smaller LDL particles adopted more ordered conformations and engaged in stronger protein-lipid interactions, despite a highly conserved protein composition. The observed structural heterogeneity suggested that variations in lipid composition may contribute to particle-size-dependent differences. Therefore, lipidomic analysis was further performed to elucidate the compositional basis underlying LDL structural diversity. Total of 1084 lipid molecular species identified across the five LDL fractions. The medium-sized LDL was relatively enriched in sphingolipids, the largest LDL contained the highest proportions of cholesterol and bile acids, and the smallest LDL showed higher relative abundances of free fatty acids and lysophosphatidylcholines. These findings indicate that remodeling of the phospholipid monolayer shell across different-sized LDL particles is driven by the geometric packing of wedge-shaped and inverted-wedge-shaped lipid molecules. This study provides a systematic understanding of the structural and compositional heterogeneity of egg yolk LDL and offers a basis for its targeted fractionation and further utilization.