Combined data from LDL composition and size measurement are compatible with a discoid particle shape

Tom Teerlink, Peter G. Scheffer, Stephan J.L. Bakker, and Robert J. Heine

Clinical Chemistry, VU University Medical Center, Amsterdam 1007 MB

Corresponding Author: t.teerlink{at}vumc.nl

The size of LDL is usually reported as particle diameter, with the implicit assumption that it is a spherical particle. On the other hand, data obtained by cryo-electron microscopy (cryo-EM) and crystallographic analysis suggest that LDL shape may be discoid, implying that two dimensions are needed to describe its size, i.e. diameter and height. We have investigated LDL particle geometry by combining data on LDL lipid composition with size measurement. Mean LDL diameter of 160 samples was measured by high performance gel-filtration chromatography (HPGC) and LDL particle volume was calculated from its lipid composition. Assuming a spherical shape, diameters calculated from volume correlated poorly with values obtained by HPGC (R² = 0.36). Assuming a discoid shape, particle height was calculated from volume and HPGC-diameter. Diameter (20.9 ± 0.5 nm) and height (12.1 ± 0.8 nm) corresponded closely to reported cryo-EM data. Diameter and height were not significantly related to each other (r = 0.14; P = 0.09) and accounted for 77% and 23% of the variation in particle volume, respectively. In multivariate regression models, LDL core lipids were the main independent determinants of height (R² = 0.83), whereas free cholesterol in the shell, which contributes only 5 - 9% to LDL mass, was the main determinant of diameter (R² = 0.54). We conclude that combined data from composition and size measurements are compatible with a discoid particle shape and propose a structural model for LDL in which free cholesterol plays a major role in determining particle shape and diameter.

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