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

Proceedings of the National Academy of Sciences of the United States of America 2024 Mar 12

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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 H[Formula: see text]O/D[Formula: see text]O isotope effect on the hydrogen-bond strength in water to investigate the role of hydration in collagen self-assembly. We dissolve collagen in H[Formula: see text]O and D[Formula: see text]O 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 D[Formula: see text]O than in H[Formula: see text]O, and collagen in D[Formula: see text]O self-assembles into much thinner fibrils, that form a more inhomogeneous and softer network, with a fourfold reduction in elastic modulus when compared to H[Formula: see text]O. Combining spectroscopic measurements with atomistic simulations, we show that collagen in D[Formula: see text]O is less hydrated than in H[Formula: see text]O. 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.

Citation

Giulia Giubertoni, Liru Feng, Kevin Klein, Guido Giannetti, Luco Rutten, Yeji Choi, Anouk van der Net, Gerard Castro-Linares, Federico Caporaletti, Dimitra Micha, Johannes Hunger, Antoine Deblais, Daniel Bonn, Nico Sommerdijk, Andela Šarić, Ioana M Ilie, Gijsje H Koenderink, Sander Woutersen. Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration. Proceedings of the National Academy of Sciences of the United States of America. 2024 Mar 12;121(11):e2313162121