Development of tunable DNA-based material technology

项目摘要/摘要 在生物医学领域，人们正在努力研究多种细胞过程，包括细胞-细胞。 通讯、细胞-基质相互作用、细胞信号、药理作用和分化等等 一些。众所周知，细胞培养系统复制本地细胞环境越紧密， 培养的细胞将越接近地模拟它们的自然行为。认识到这一点，多年来，各种形式 三维文化战略的出现是一种优于2D文化的进步。最多的 有希望的方法包括那些在其结构、机械结构、 和组合物，从而提供理想的生物信号和细胞识别部位，促进 正常的细胞行为。为了实现这一目标，这项技术发展建议的重点是开发一种 可调节的、生物活性的、基于DNA的水凝胶平台，可以满足这些组织的特定要求，并用于 体外细胞培养的进展。这项材料技术意义重大，因为基于DNA的水凝胶平台 消除了复杂的化学相互作用的需要，并利用快速自组装和 当DNA与细胞外基质蛋白胶原蛋白形成络合物时，自发形成的纤维。此外，这一点 Platform利用功能DNA适配子使水凝胶具有生物活性。这项技术有望推动 对于生物医学研究人员的广泛社区来说，细胞功能更具原生性和可重复性。至 为了实现我们的目标，我们项目的目标是1)检查可用DNA实现的大宗材料特性- 胶原基水凝胶；以及2)用生物活性DNA适配子功能化DNA水凝胶。我们的研究将 与常用的水凝胶进行比较，我们将通过验证研究来展示生物影响。 上述目标的完成有望揭示DNA-胶原的全部广度和潜力 基于材料以模拟组织特异性ECM，并作为广泛的生物医学的材料平台 学习。我们打算开发一个具有明确合成条件的DNA-胶原基质文库 能够调节涉及细胞-细胞的一系列细胞反应的机械性能和生物活性 相互作用，细胞-基质相互作用，药理学研究，模拟细胞的健康或疾病状态， 对不同的细胞表型、干细胞研究和一系列其他基础研究的机械洞察 组织特有的细胞行为。

Project Summary/Abstract Within the biomedical field there is great effort to study a multitude of cell processes, including cell-cell communication, cell-matrix interactions, cell signaling, pharmacological effects, and differentiation to name a few. It is widely known that the more closely the cell culture system replicates the native cellular environment, the more closely the cultured cells will model their native behaviors. Knowing this, over the years, various forms of three-dimensional culture strategies have emerged as a superior advancement over 2D culture. The most promising approaches include those that mimic the native extracellular matrix, in its architecture, mechanics, and composition, thereby providing the ideal biological signaling and cellular recognition sites that promote normal cell behavior. Towards this goal, the focus of this technology development proposal is to develop a tunable, bioactive, DNA-based hydrogel platform that can meet these tissue specific requirements and serves to advance in vitro cell culture. This material technology is significant because the DNA-based hydrogel platform eliminates the need for complex chemical interactions and takes advantage of the rapid self-assembly and spontaneous fibril formation that occurs when DNA is complexed with ECM protein collagen. In addition, this platform utilizes functional DNA aptamers to render the hydrogel bioactive. This technology is poised to promote cellular functions that are more native and reproducible to a broad community of biomedical researchers. To achieve our goals, the aims of our project are 1) Examine to bulk material properties achievable with DNA- collagen based hydrogels; and 2) Functionalize DNA-hydrogels with bioactive DNA aptamers. Our studies will be compared to commonly used hydrogels and we will demonstrate biological impact through validation studies. Completion of the above-described aims is expected to reveal the full breadth and potential of DNA-collagen based materials to mimic tissue specific ECM and serve as a material platform for a broad array of biomedical studies. We intend to develop a library of DNA-collagen bulk matrix with well-defined synthesis conditions capable of tunable mechanical properties and bioactivity for a range of cell responses involved cell-cell interactions, cell-matrix interactions, pharmacological studies, modelled health or disease states of cells, mechanistic insight into varied cell phenotypes, stem cell studies, and an array of other fundamental studies of tissue specific cell behaviors.