Structured materials for the study of biomolecular and cell-substrate interactions

微米和纳米级表面性质（例如，拓扑学、生物化学功能）在体内生物分子和细胞相互作用中起关键作用。在生物小生境中遇到的生物化学线索的地形特征和空间分布的组合驱动细胞粘附、增殖、表达某些表型并分化成特定的细胞谱系。为了在体外研究相关的生物相互作用，需要通过形貌（表面结构的大小和周期性）和生物材料的空间分布来创建模拟自然微环境的人工微环境的方法。在过去的十年中，已经开发了微制造方法来创建通过生物材料的形貌或图案传达生物功能的结构化材料。尽管这些方法取得了成功，但存在关键的限制，这些限制阻止了它们用于快速产生具有可调特征的结构化表面和形成不能耐受干燥的生物材料的图案（例如，细胞和脂质）。 该研究计划的重点是开发新的方法来创建微和纳米结构材料，用于生物分子和细胞表面相互作用的研究，并通过概念验证应用展示这些方法的实用性。我们的研究将解决当前制造方法的关键限制，包括（a）缺乏简易的方法来制造具有在微米至纳米尺度可调的特征的结构化表面，（B）无法以复杂图案存款生物材料（即生物分子和细胞），以及（c）无法图案化不能耐受干燥的多种生物材料。我们预计，从长远来看，在水性环境下以复杂分布模式化生物材料，特别是细胞的能力将促进对组织内细胞功能和命运至关重要的细胞-细胞相互作用的研究。总的来说，拟议研究的成果将有助于产生关于生物系统的知识，提供一个多学科的环境，为培训HQP提供独特的机会，并将建立一个尖端的研究计划。

Micro- and nanoscale surface properties (e.g., topography, biochemical function) play a critical role in biomolecular and cellular interactions in vivo. The combination of topographical features and spatial distribution of biochemical cues encountered in biological niches drive cells to adhere, proliferate, express certain phenotypes, and differentiate into specific cell lineages. To study relevant biological interactions in vitro, methods are needed to create artificial microenvironments that mimic natural ones through topography (size and periodicity of surface structures) and the spatial distribution of biomaterials. Over the past decade, microfabrication approaches have been developed to create structured materials that convey biological function through topography or patterns of biomaterials. Despite the success of these approaches, key limitations exist that prevent their use in the rapid creation of structured surfaces with tuneable features and in the formation of patterns of biomaterials that cannot tolerate drying (e.g., cells and lipids). This research program focuses on developing novel methods to create micro- and nanostructured materials for the study of biomolecular and cell-surface interactions and demonstrating the utility of these methods through proof-of-concept applications. Our research will solve critical limitations of current fabrication methods, including (a) the lack of facile methods to fabricate structured surfaces with features tuneable in the micro- to nanometer scale, (b) the inability to deposit biomaterials (i.e. biomolecules and cells) in complex patterns, and (c) the inability to pattern multiple biomaterials that cannot tolerate drying. We anticipate that in the long-term the ability to pattern biomaterials, particularly cells, in complex distributions under aqueous environments will facilitate the study of cell-cell interactions that are critical to cellular function and fate within tissues. Overall, the outcomes of the proposed research will help generate knowledge on biological systems, provide a multidisciplinary environment that offers unique opportunities for training HQP, and will establish a cutting-edge research program.