UNS: Nanotopographical Memory Modulates Stem Cell Fate

1511759杨勇 使用平的、硬的塑料表面的常规细胞培养方法不能概括特征（例如，硬度和纳米形貌）的细胞外基质（ECM）与细胞在体内相互作用。 因此，细胞在这种表面上的行为显著偏离其体内对应物。迫切需要将ECM特征纳入干细胞培养技术中。本研究的目标是通过研究干细胞的纳米形貌记忆效应来推进下一代细胞培养技术。ECM/基底纳米形貌和刚度严重影响体内许多发育、生理和病理过程，并对体外细胞行为和干细胞命运决定产生深远影响。 假设干细胞可以保留来自过去培养环境的纳米形貌信息，并且纳米形貌记忆可以影响干细胞未来的命运决定。这项研究的目的是验证这一假设，并阐明纳米地形记忆效应的潜在机制。以人骨髓间充质干细胞（human mesenchymal stem cells，hMSCs）为模型细胞，研究纳米形貌记忆效应的三个研究目标：（1）利用纳米形貌调控Yes相关蛋白（雅普）的细胞内定位;（2）研究纳米形貌记忆效应;（3）阐明纳米形貌记忆效应的机制。这项研究将促进对发育和病理过程中细胞机械传导和干细胞可塑性的理解。它将引起人们对体外培养过程中意外的纳米地形记忆效应的关注，这可能会影响干细胞的功能和分化。这项研究将有助于下一代干细胞培养技术的发展，并为再生医学植入物和医疗器械的新生物材料和细胞基质界面的设计提供见解。此外，一个合作的，跨学科的，将建立一个通过研究学习的系统，为促进西弗吉尼亚州的纳米生物技术教育提供基本的基础设施。CBET的生物技术和生物化学工程项目的这个奖项是共同的，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准。

1511759Yang, Yong Conventional cell culture methods using flat, stiff plastic surfaces do not recapitulate characteristics (e.g., stiffness and nanotopography) of the extracellular matrix (ECM) with which cells interact in vivo. Therefore, cell behavior on such surfaces significantly deviate from their in vivo counterparts. There is a pressing need to incorporate the ECM characteristics into stem cell culture technologies. The goal of this research is to advance next-generation cell culture technologies by investigating nanotopographical memory effects of stem cells.ECM/substrate nanotopography and stiffness critically influence numerous developmental, physiological and pathological processes in vivo, and have a profound influence on cell behavior and stem cell fate decision in vitro. It is hypothesized that stem cells can retain nanotopographical information from past culture environments and the nanotopographical memory can influence future fate decision of stem cells. The objective of the proposed research is to test this hypothesis and to delineate the underlying mechanism of nanotopographical memory effects. Three research objectives using human mesenchymal stem cells (hMSCs) as model cells are proposed to study the nanotopographical memory effects: (1) Regulate Yes-associated protein (YAP) intracellular localization by using nanotopography, (2) Validate nanotopographical memory effects, and (3) Delineate the underlying mechanism of nanotopographical memory effects. This research will advance the understanding of cellular mechanotransduction and stem cell plasticity during developmental and pathological processes. It will call attention to unintended nanotopographical memory effects during in vitro culture, which may affect stem cell function and differentiation. This research will contribute to the development of next-generation stem cell culture technologies, and provide insight into the design of new biomaterials and the cell-substrate interfaces of implants and medical devices for regenerative medicine. In addition, a collaborative, cross-disciplinary, learn-through-research system will be established to provide the basic infrastructure to promote nanobiotechnology education in West Virginia.This award by the Biotechnology and Biochemical Engineering Program of CBET is co-funded by the Biomaterials Program of the Division of Materials Research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.