Sugars and polyols inhibit fibrillogenesis of type I collagen by disrupting hydrogen-bonded water bridges between the helices.

To better understand the mechanism of collagen fibrillogenesis, we studied how various sugars and polyols affect the formation and stability of collagen fibers. We combined traditional fiber assembly assays with direct measurement of the interaction between collagen triple helices in fibers by osmotic stress and X-ray diffraction. We found that the effects of sugars and polyols were highly specific with respect to small structural differences between these solutes. For example, 1,2-propane diol only weakly inhibited the fiber assembly and practically did not affect the interaction between collagen helices in fibers. At the same concentration, 1,3-propane diol eliminated the attraction between collagen helices and strongly suppressed fibrillogenesis. The two diols have the same atomic composition and differ only by the position of one of their hydroxyls. Still, their ability to inhibit fiber assembly differs by more than an order of magnitude, as judged by protein solubility. We argue that this is because collagen fibrillogenesis requires formation of hydrogen-bonded water clusters bridging recognition sites on the opposing helices. The ability of various sugars and polyols to inhibit the fiber assembly and to destabilize existing fibers is determined by how efficiently these solutes can compete with water for crucial hydrogen bonds and, thus, disrupt the water bridges. The effect of a sugar or a polyol appears to be strongly dependent on the specific stereochemistry of the solute hydroxyls that defines the preferred hydrogen-bonding pattern of the solute.