Reconsideration of hydrophobic lipid distributions in lipoprotein particles

Abstract

Lipoprotein particles are commonly known as micellar aggregates with hydrophobic lipids located within the core and amphipathic molecules in the surface. Using a new structural model for optimizing the distribution of hydrophobic lipids, namely triglyceride (TG) and cholesterol ester (CE) molecules, we reveal that particle size-dependent proportion of these ‘core lipids’ may locate in the surface of lipoprotein particles. The composition of the particles also strongly influences the actual molecular content of the surface. For example, in high-density lipoprotein (HDL) particles the percentage of CEs of all surface lipids is between 13% and 27% due to the high tendency of CEs to locate in the surface and the high concentration of CEs in the particles. Conversely, although the percentage of TG molecules in the surface of HDL particles is also high, approximately 60% as for CE, the percentage of TGs of all surface lipids is low, only up to 5%, because HDL particles have a low-TG concentration. These structural models provide an intuitive and coherent structural rationale for various metabolic cascades in lipoprotein metabolism with the catalytic enzyme action and molecular binding for transport proteins taking place at the surface of the particles.