Nuclear Magnetic Resonance and Metadynamics Simulations Reveal the Atomistic Binding of l -Serine and O-Phospho- l -Serine at Disordered Calcium Phosphate Surfaces of Biocements

Renny Mathew, Baltzar Stevensson, Michael Pujari-Palmer, Christopher S. Wood, Phillip R.A. Chivers, Christopher D. Spicer, Hélène Autefage, Molly M. Stevens, Håkan Engqvist, Mattias Edén*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Interactions between biomolecules and structurally disordered calcium phosphate (CaP) surfaces are crucial for the regulation of bone mineralization by noncollagenous proteins, the organization of complexes of casein and amorphous calcium phosphate (ACP) in milk, as well as for structure-function relationships of hybrid organic/inorganic interfaces in biomaterials. By a combination of advanced solid-state NMR experiments and metadynamics simulations, we examine the detailed binding of O-phospho-l-serine (Pser) and l-serine (Ser) with ACP in bone-adhesive CaP cements, whose capacity of gluing fractured bone together stems from the close integration of the organic molecules with ACP over a subnanometer scale. The proximity of each carboxy, aliphatic, and amino group of Pser/Ser to the Ca2+ and phosphate species of ACP observed from the metadynamics-derived models agreed well with results from heteronuclear solid-state NMR experiments that are sensitive to the 13C-31P and 15N-31P distances. The inorganic/organic contacts in Pser-doped cements are also contrasted with experimental and modeled data on the Pser binding at nanocrystalline HA particles grown from a Pser-bearing aqueous solution. The molecular adsorption is driven mainly by electrostatic interactions between the negatively charged carboxy/phosphate groups and Ca2+ cations of ACP, along with H bonds to either protonated or nonprotonated inorganic phosphate groups. The Pser and Ser molecules anchor at their phosphate/amino and carboxy/amino moieties, respectively, leading to an extended molecular conformation across the surface, as opposed to an "upright standing"molecule that would result from the binding of one sole functional group.

Original languageEnglish
Pages (from-to)8815–8830
Number of pages16
JournalChemistry of Materials
Issue number19
Early online date26 Sept 2022
Publication statusPublished - 11 Oct 2022

Bibliographical note

Funding Information:
This work was supported by the Swedish Foundation for Strategic Research (funder ID 501100001729; project RMA15–0110). The computations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at NSC, partially funded by the Swedish Research Council through grant agreement no. 2018-05973. C.S.W. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement 747414. P.R.A.C. was financially supported by the Wenner-Gren Foundations. We thank Kjell Jansson and Zoltán Bacsik for TEM and surface-area measurements, respectively, and Debashis Majhi for help with processing some of the NMR spectra.

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.

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