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Calcium materials, such as calcium carbonate, are produced in natural and industrial settings that range from oceanic to biomedical. An array of biological and biomimetic template molecules have been employed in controlling and understanding the mineralization reaction but have largely focused on small molecule additives or disordered polyelectrolytes. DNA aptamers are synthetic and programmable biomolecules with polyelectrolyte characteristics but with predictable and controllable secondary structure akin to native extracellular moieties. This work demonstrates for the first time the influence of DNA aptamers with known G-quadruplex structures on calcium carbonate mineralization. Aptamers demonstrate kinetic inhibition of mineral formation, sequence and pH-dependent uptake into the mineral, and morphological control of the primarily calcite material in controlled solution conditions. In reactions initiated from the complex matrix of ocean water, DNA aptamers demonstrated enhancement of mineralization kinetics and resulting amorphous material. This work provides new biomimetic tools to employ in controlled mineralization and demonstrates the influence that template secondary structure can have in material formation.
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Equilibrium interactions of biomimetic DNA aptamers produce intrafibrillar calcium phosphate mineralization of collagen
Native and biomimetic DNA structures have been demonstrated to impact materials synthesis under a variety of conditions but have only just begun to be explored in this role compared to other biopolymers such as peptides, proteins, polysaccharides, and glycopolymers. One selected DNA aptamer has been explored in calcium phosphate and calcium carbonate mineralization, demonstrating sequence-dependent control of kinetics, morphology, and crystallinity. This aptamer is here applied to a biologically-relevant bone model system that uses collagen hydrogels. In the presence of the aptamer, intrafibrillar collagen mineralization is observed compared to negative controls and a positive control using well-studied poly-aspartic acid. The mechanism of interaction is explored through affinity measurements, kinetics of calcium uptake, and kinetics of aptamer uptake into the forming mineral. There is a marked difference observed between the selected aptamer containing a G-quadruplex secondary structure compared to a control sequence with no G-quadruplex. It is hypothesized that the equilibrium interaction of the aptamer with calcium-phosphate precursors and with the collagen itself leads to slow kinetic mineral formation and a morphology appropriate to bone. This points to new uses for DNA aptamers in biologically-relevant mineralization systems and the possibility of future biomedical applications.
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- Award ID(s):
- 1904460
- PAR ID:
- 10498895
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Acta Biomaterialia
- ISSN:
- 1742-7061
- Subject(s) / Keyword(s):
- collagen DNA aptamer mineralization bone
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1016/j.actbio.2024.03.018
