Pipis Nikolaos, Stewart Kevin A, Tabatabaei Mohammad, Williams Lakiesha N, Allen Josephine B
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611, United States.
George & Josephine Butler Polymer Research Laboratory, Department of Chemistry, Center for Macromolecular Science and Engineering, University of Florida, Gainesville, Florida 32611, United States.
ACS Omega. 2024 Jul 11;9(29):32052-32058. doi: 10.1021/acsomega.4c04104. eCollection 2024 Jul 23.
Nucleic acid-collagen complexes (NACCs) are a self-assembled biomimetic fibrillary platform arising from the spontaneous complexation of single-stranded DNA (ssDNA) oligonucleotides and collagen. NACCs merge the extracellular matrix functionality of collagen with the tunable bioactivity of ssDNA as aptamers for broad biomedical applications. We hypothesize that NACCs offer a hierarchical architecture across multiple length scales that significantly varies compared to native collagen. We investigate this using atomic force microscopy and electron microscopy (transmission electron microscopy and cryogenic electron microscopy). Results demonstrate key topographical differences induced by adding ssDNA oligonucleotides to collagen type I. NACCs form a dense network of intertwined collagen fiber bundles in the microscale and nanoscale while retaining their characteristic D-band periodicities (∼67 nm). Additionally, our exploration of thermodynamic parameters governing the interaction indicates an entropically favorable NACC formation driven by ssDNA. Thermal analysis demonstrates the preservation of collagen's triple helical domains and a more stabilized polypeptide structure at higher temperatures than native collagen. These findings offer important insights into our understanding of the ssDNA-induced complexation of collagen toward the further establishment of structure-property relationships in NACCs and their future development into practical biomaterials. They also provide pathways for manipulating and enhancing collagenous matrices' properties without requiring complex chemical modifications or fabrication procedures.
核酸 - 胶原蛋白复合物（NACCs）是一种自组装的仿生纤维状平台，由单链DNA（ssDNA）寡核苷酸与胶原蛋白的自发络合产生。NACCs将胶原蛋白的细胞外基质功能与ssDNA作为适配体的可调生物活性相结合，用于广泛的生物医学应用。我们假设NACCs提供了一种跨多个长度尺度的层次结构，与天然胶原蛋白相比有显著差异。我们使用原子力显微镜和电子显微镜（透射电子显微镜和低温电子显微镜）对此进行研究。结果表明，向I型胶原蛋白中添加ssDNA寡核苷酸会引起关键的形貌差异。NACCs在微米级和纳米级形成了由交织的胶原纤维束组成的密集网络，同时保留了其特征性的D带周期性（约67纳米）。此外，我们对控制相互作用的热力学参数的探索表明，由ssDNA驱动的NACCs形成在熵方面是有利的。热分析表明，胶原蛋白的三螺旋结构域得以保留，并且在比天然胶原蛋白更高的温度下具有更稳定的多肽结构。这些发现为我们理解ssDNA诱导的胶原蛋白络合提供了重要见解，有助于进一步建立NACCs中的结构 - 性能关系及其未来发展为实用生物材料。它们还提供了在不需要复杂化学修饰或制造程序的情况下操纵和增强胶原基质性能的途径。
