Equilibrium interactions of biomimetic DNA aptamers produce intrafibrillar calcium phosphate mineralization of collagen
Equilibrium interactions of biomimetic DNA aptamers produce intrafibrillar calcium phosphate mineralization of collagen
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DOI：
10.1016/j.actbio.2024.03.018
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发表时间：
2024-04-23
影响因子：
9.7
通讯作者：
Gerdon，Aren E.
中科院分区：
文献类型：
--
作者：
Patoine，Kassidy;Ta，Kristy;Gerdon，Aren E.
天然和仿生 DNA 结构已被证明可以在各种条件下影响材料合成，但与肽、蛋白质、多糖和糖聚合物等其他生物聚合物相比，其作用才刚刚开始被探索。一种选定的 DNA 适体已在磷酸钙和碳酸钙矿化中进行了探索，证明了动力学、形态和结晶度的序列依赖性控制。该适体应用于使用胶原水凝胶的生物相关骨模型系统。在存在适体的情况下，与阴性对照和使用经过充分研究的聚天冬氨酸的阳性对照相比，观察到原纤维内胶原矿化。通过亲和力测量、钙吸收动力学和适体吸收形成矿物质的动力学来探索相互作用的机制。与不含 G-四链体的对照序列相比，在所选的包含 G-四链体二级结构的适体之间观察到显着差异。据推测，适体与磷酸钙前体和胶原本身的平衡相互作用导致缓慢的动态矿物质形成和适合骨的形态。这指出了 DNA 适体在生物相关矿化系统中的新用途以及未来生物医学应用的可能性。重要性声明胶原蛋白是与磷酸钙矿化形成耐用骨骼的蛋白质结构成分。结晶磷酸钙必须注入到整个胶原纤维结构中才能产生坚固的材料。该过程得到与磷酸钙前体和胶原蛋白相互作用的可溶性蛋白质的协助，并且已被提议遵循聚合物诱导液体前体（PILP）模型。进一步了解该模型并通过合成仿生分子控制该过程可能在生物医学、恢复过程中具有显着优势。具有特定二级结构的合成 DNA 适体首次被证明可以影响和指导胶原蛋白矿化。对该过程的机制进行了研究，证明了 DNA 适体、磷酸钙前体和胶原蛋白之间的重要平衡。
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.Statement of significanceCollagen is the protein structural component that mineralizes with calcium phosphate to form durable bone. Crystalline calcium phosphate must be infused throughout the collagen fiber structure to produce a strong material. This process is assisted by soluble proteins that interact with both calcium phosphate precursors and the collagen protein and has been proposed to follow a polymer-induce liquid precursor (PILP) model. Further understanding of this model and control of the process through synthetic, biomimetic molecules could have significant advantages in biomedical, restorative procedures. For the first time, synthetic DNA aptamers with specific secondary structures are here shown to influence and direct collagen mineralization. The mechanism of this process has been studied to demonstrate an important equilibrium between the DNA aptamer, calcium phosphate precursors, and collagen.