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A computational study on strontium ion modified hydroxyapatite-fibronectin interactions

Basu, S and Basu, B and Maiti, PK (2022) A computational study on strontium ion modified hydroxyapatite-fibronectin interactions. In: Physical Chemistry Chemical Physics, 24 (45). pp. 27989-28002.

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Official URL: https://doi.org/10.1039/d2cp04454d


Protein adsorption is the first key step in cell-material interactions. The initial phase of such an adsorption process can only be probed using modelling approaches like molecular dynamics (MD) simulations. Despite a large number of studies on the adsorption behaviour of proteins on different biomaterials including calcium phosphates (CaP), little attention has been paid towards the quantitative assessment of the effects of various physicochemical influencers like surface modification, pH, and ionic strength. In the case of doped CaPs, surface modification through isomorphic substitution of foreign ions inside the apatite structure is of particular interest in the context of protein-HA interactions, as it is widely used to tailor the biological response of HA. Given this background, we present here the molecular-level understanding of the fibronectin (FN) adsorption mechanism and kinetics on a Sr2+-doped hydroxyapatite, HA, (001) surface at 300 K by means of all-atom molecular dynamics simulations. Electrostatic interactions involved in the adsorption of FN on HA were found to be significantly modified due to Sr2+ doping into the apatite lattice. In harmony with the published experimental observations, the Sr-doped surfaces were found to better support FN adhesion compared to pure HA, with 10 mol Sr-doped HA exhibiting the best FN adsorption. The observed altered adsorption behaviour of FN on Sr-doped HA was correlated with the Hofmeister effect. Moreover, the non-monotonous trend of the FN-material interaction energy can be attributed to the spatial rearrangement of the functional groups (PO43�, OH�) in the apatite crystal. Sr2+ ions also influence the stability of the secondary structure of FN, as observed from the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analysis. The presence of Sr2+ enhances the flexibility of specific residues (residue nos. 20-44, 74-88) of the FN module. Rupture forces to disentangle FN from the biomaterial surface, obtained from steered molecular dynamics (SMD) simulations, were found to corroborate well with the results of equilibrium MD simulations. One particular observation is that the availability of an RGD motif (Arginine-Glycine-aspartate sequence, which interacts with cell surface receptor integrin to form a focal adhesion complex) for the interaction with cell surface receptor integrin is not significantly influenced by Sr2+ substitution. © 2022 The Royal Society of Chemistry.

Item Type: Journal Article
Publication: Physical Chemistry Chemical Physics
Publisher: Royal Society of Chemistry
Additional Information: The copyright for this article belongs to Royal Society of Chemistry.
Department/Centre: Division of Chemical Sciences > Materials Research Centre
Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 04 Jan 2023 05:23
Last Modified: 04 Jan 2023 05:23
URI: https://eprints.iisc.ac.in/id/eprint/78695

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