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 stu died how various sugars and polyols affect the formation and stability of collagen fibers. We combined traditional fiber assembly assays wit h direct measurement of the interaction between collagen triple helice s in fibers by osmotic stress and X-ray diffraction. We found that the effects of sugars and polyols were highly specific with respect to sm all structural differences between these solutes. For example, 1,2-pro pane 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 betwee n collagen helices and strongly suppressed fibrillogenesis. The two di ols have the same atomic composition and differ only by the position o f one of their hydroxyls. Still, their ability to inhibit fiber assemb ly differs by more than an order of magnitude, as judged by protein so lubility. We argue that this is because collagen fibrillogenesis requi res formation of hydrogen-bonded water clusters bridging recognition s ites on the opposing helices. The ability of various sugars and polyol s 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 effe ct of a sugar or a polyol appears to be strongly dependent on the spec ific stereochemistry of the solute hydroxyls that defines the preferre d hydrogen-bonding pattern of the solute.