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

微纳尺度的表面性质(如形貌、生化功能)在体内生物分子和细胞相互作用中起着至关重要的作用。生物利基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黏附、增殖、表达某些表型，并分化为特定的细胞谱系。为了在体外研究相关的生物相互作用，需要通过地形(表面结构的大小和周期性)和生物材料的空间分布来创造模拟自然微环境的方法。在过去的十年里，微制造方法已经被开发出来，以创建通过生物材料的形貌或图案来传达生物功能的结构化材料。尽管这些方法取得了成功，但关键的局限性阻碍了它们在快速创建具有可调特征的结构化表面以及形成不耐干燥的生物材料(例如细胞和脂质)图案方面的使用。 这项研究计划的重点是开发新的方法来创建微结构和纳米结构材料，用于研究生物分子和细胞表面的相互作用，并通过概念验证应用来展示这些方法的实用性。我们的研究将解决目前制造方法的严重局限性，包括(A)缺乏简便的方法来制造具有微米到纳米级可调特征的结构化表面，(B)无法以复杂的图案沉积生物材料(即生物分子和细胞)，以及(C)无法对多种不耐干燥的生物材料进行图案制作。我们预计，从长远来看，在水环境下以复杂分布塑造生物材料，特别是细胞的能力，将促进对细胞功能和组织内命运至关重要的细胞-细胞相互作用的研究。总体而言，拟议研究的结果将有助于产生关于生物系统的知识，提供一个为培训HQP提供独特机会的多学科环境，并将建立一个尖端研究计划。

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.