Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration

• 成果类型: Article
• 署名作者: Giubertoni, Giulia; Feng, Liru; Klein, Kevin; Giannetti, Guido; Rutten, Luco; Choi, Yeji; van der Net, Anouk; Castro-Linares, Gerard; Caporaletti, Federico; Micha, Dimitra; Hunger, Johannes; Deblais, Antoine; Bonn, Daniel; Sommerdijk, Nico; Saric, Andela; Ilie, Ioana M.; Koenderink, Gijsje H.; Woutersen, Sander
• 署名单位: University of Amsterdam; Institute of Science & Technology - Austria; University of London; University College London; Radboud University Nijmegen; Max Planck Society; Delft University of Technology; University of Amsterdam; University of Amsterdam; University of Amsterdam
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13724
• DOI: 10.1073/pnas.2313162121
• 发表日期: 2024-03-12
• 关键词: molecular-dynamics; crystal-structure; osteogenesis imperfecta; fibril; fibrillogenesis; MODEL; bone; h2o; STABILITY; mechanism

摘要

Water is known to play an important role in collagen self -assembly, but it is still largely unclear how water-collagen interactions influence the assembly process and determine the fibril network properties. Here, we use the H2O/D2O isotope effect on the hydrogen -bond strength in water to investigate the role of hydration in collagen selfassembly. We dissolve collagen in H2O and D2O and compare the growth kinetics and the structure of the collagen assemblies formed in these water isotopomers. Surprisingly, collagen assembly occurs ten times faster in D2O than in H2O, and collagen in D2O self -assembles into much thinner fibrils, that form a more inhomogeneous and softer network, with a fourfold reduction in elastic modulus when compared to H2O. Combining spectroscopic measurements with atomistic simulations, we show that collagen in D2O is less hydrated than in H2O. This partial dehydration lowers the enthalpic penalty for water removal and reorganization at the collagen-water interface, increasing the self -assembly rate and the number of nucleation centers, leading to thinner fibrils and a softer network. Coarse -grained simulations show that the acceleration in the initial nucleation rate can be reproduced by the enhancement of electrostatic interactions. These results show that water acts as a mediator between collagen monomers, by modulating their interactions so as to optimize the assembly process and, thus, the final network properties. We believe that isotopically modulating the hydration of proteins can be a valuable method to investigate the role of water in protein structural dynamics and protein self -assembly.