The interactions between cholesterol and other membrane molecules determine important membrane properties. It was shown that even small changes in the molecular structure of cholesterol have a crucial influence on these interactions. We recently reported that in addition to alterations in the tetracyclic ring structure, the iso-branched side chain of cholesterol also has a significant impact on membrane properties (Scheidt H. et al. 2013 Angew. Chem. Int. Ed. Engl. 52, 12848-12851). Here we used synthetic cholesterol analogs to investigate the influence of an unbranched aliphatic side chain of different length. The 2H NMR order parameter of the phospholipid chains and therefore the molecular packing of the phospholipid molecules shows a significant dependence on the sterol’s alkyl side chain length, while , membrane permeation studied by a dithionite ion permeation assay and lateral diffusion measured by 1H MAS pulsed field gradient NMR are less influenced. To achieve the same molecular packing effect similar to that of an iso-branched aliphatic side chain, a longer unbranched side chain (n-dodecyl instead of n-octyl) at C17 of cholesterol is required. Obviously, sterols having a branched iso- alkyl chain with two terminal methyl groups exhibit altered cholesterol-phospholipid-interactions compared to analogous molecules with a straight unbranched chain.

The interactions between cholesterol and other membrane molecules determine important membrane properties. It was shown that even small changes in the molecular structure of cholesterol have a crucial influence on these interactions. We recently reported that in addition to alterations in the tetracyclic ring structure, the iso-branched side chain of cholesterol also has a significant impact on membrane properties (Scheidt H. et al. 2013 Angew. Chem. Int. Ed. Engl. 52, 12848-12851). Here we used synthetic cholesterol analogs to investigate the influence of an unbranched aliphatic side chain of different length. The 2H NMR order parameter of the phospholipid chains and therefore the molecular packing of the phospholipid molecules shows a significant dependence on the sterol’s alkyl side chain length, while , membrane permeation studied by a dithionite ion permeation assay and lateral diffusion measured by 1H MAS pulsed field gradient NMR are less influenced. To achieve the same molecular packing effect similar to that of an iso-branched aliphatic side chain, a longer unbranched side chain (n-dodecyl instead of n-octyl) at C17 of cholesterol is required. Obviously, sterols having a branched iso- alkyl chain with two terminal methyl groups exhibit altered cholesterol-phospholipid-interactions compared to analogous molecules with a straight unbranched chain.