Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai200237, China.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai200011, China.
ACS Appl Mater Interfaces. 2022 May 11;14(18):20739-20748. doi: 10.1021/acsami.2c03265. Epub 2022 Apr 29.
Interlocked DNA nanostructures perform programmable movements in nanoscales such as sliding, contraction, and expansion. However, utilizing nanoscaled interlocked movements to regulate the functions of larger length scaled matrix and developing their applications has not yet been reported. Herein we describe the assembly of DNA-based daisy chain rotaxane nanostructure (DNA-DCR) composed of two hollow DNA nanostructures as macrocycles, two interlocked axles and two triangular prism-shaped DNA structures as stoppers, in which three mechanical states─fixed extended state (FES), sliding state (SS), and fixed contracted state (FCS)─are characterized by using toehold-mediated strand displacement reaction (SDR). The DNA-DCRs are further used as nanocomposites and introduced into hydrogel matrix to produce interlocked hydrogels, which shows modulable stiffness by elongating the interlocked axles to regulate the hydrogel swelling with hybridization chain reaction (HCR) treatment. Then the DCR-hydrogels are employed as dynamic biointerfaces for human mesenchymal stem cells (hMSCs) adhesion studies. First, hMSCs showed lower cell density on bare DCR-hydrogel treated with HCR-initiated swelling for stiffness decreasing. Second, the cell adhesion ligand (RGD) modified DNA-DCRs are constructed for hydrogel functionalization. DCR hydrogel endows the mobility of RGDs by switching the mechanical states of DNA-DCR. HMSCs showed increased cell density on DCR hydrogel than on DCR hydrogel. Therefore, our DNA-DCR nanocomposite hydrogel exhibit dual-programmable performances including swelling adjustment and offering sliding for incorporated ligands, which can be both utilized as dynamic scaffolds for regulating the stem cell adhesion. The dual-programmable cross-scale regulation from interlocked DNA nanostructures to hydrogel matrix was achieved, demonstrating a new pathway of DNA-based materials.
互锁 DNA 纳米结构在纳米尺度上进行可编程运动，如滑动、收缩和扩张。然而，利用纳米级互锁运动来调节较大长度尺度基质的功能并开发其应用尚未见报道。在此，我们描述了由两个空心 DNA 纳米结构作为大环、两个互锁轴和两个三角形棱柱形 DNA 结构作为塞子组成的基于 DNA 的雏菊链轮烷纳米结构（DNA-DCR）的组装，其中三个机械状态——固定扩展状态（FES）、滑动状态（SS）和固定收缩状态（FCS）——通过使用引发链置换反应（SDR）的结合点介导的链置换反应来表征。DNA-DCR 进一步用作纳米复合材料并引入水凝胶基质中以产生互锁水凝胶，通过延长互锁轴来调节水凝胶的溶胀并用杂交链式反应（HCR）处理来调节互锁水凝胶的可调节硬度。然后，将 DCR-水凝胶用作动态生物界面，用于人间充质干细胞（hMSC）的粘附研究。首先，在用 HCR 引发的溶胀处理后，hMSC 在裸 DCR-水凝胶上的细胞密度较低，因为硬度降低。其次，构建了用于水凝胶功能化的细胞粘附配体（RGD）修饰的 DNA-DCR。DCR 水凝胶通过切换 DNA-DCR 的机械状态赋予 RGD 的流动性。HMSCs 在 DCR 水凝胶上的细胞密度高于在 DCR 水凝胶上的细胞密度。因此，我们的 DNA-DCR 纳米复合水凝胶表现出双重可编程性能，包括溶胀调节和为结合配体提供滑动，可作为调节干细胞粘附的动态支架。从互锁 DNA 纳米结构到水凝胶基质的双重可编程跨尺度调节得以实现，展示了基于 DNA 的材料的新途径。
