Eliminating the Roughness in Cholesterol’s β-Face: Does it Matter?

[Image: see text] One of the long-standing issues surrounding cholesterol (Chol) relates to its two-faced character. In particular, the consequences of its having a rough β-face and a smooth α-face on its structural influence in cell membranes has remained elusive. In this study, direct comparisons have been made between cholesterol and a “smoothened” analog, DChol (i.e., 18,19-dinorcholesterol) using model membranes and a combination of nearest-neighbor recognition, differential scanning calorimetry, fluorescence, and monolayer measurements. Taken together, these results indicate that subtle differences exist between the interaction of these two sterols with the different states of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Chol has a greater condensing power than DChol, but only slightly so, i.e., on the order of a few tens of calories per mole.