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Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell of Interest Using Cell-Derived Biomimetic Patterning

机译:使用细胞衍生的仿生图案对用户选择的感兴趣细胞的细胞结构进行概括和调节

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摘要

Heterogeneity of cell populations can confound population-averaged measurements and obscure important findings or foster inaccurate conclusions. The ability to generate a homogeneous cell population, at least with respect to a chosen trait, could significantly aid basic biological research and development of high-throughput assays. Accordingly, we developed a high-resolution, image-based patterning strategy to produce arrays of single-cell patterns derived from the morphology or adhesion site arrangement of user-chosen cells of interest (COIs). Cells cultured on both cell-derived patterns displayed a cellular architecture defined by their morphology, adhesive state, cytoskeletal organization, and nuclear properties that quantitatively recapitulated the COIs that defined the patterns. Furthermore, slight modifications to pattern design allowed for suppression of specific actin stress fibers and direct modulation of adhesion site dynamics. This approach to patterning provides a strategy to produce a more homogeneous cell population, decouple the influences of cytoskeletal structure, adhesion dynamics, and intracellular tension on mechanotransduction-mediated processes, and a platform for high-throughput cellular assays.
机译:细胞群体的异质性可能会混淆群体平均测量值,并掩盖重要发现或得出不准确的结论。至少在选择的性状上,产生均质细胞群的能力可以极大地帮助基础生物学研究和开发高通量分析。因此,我们开发了一种基于图像的高分辨率图案化策略,以产生源自用户选择的目标细胞(COI)的形态或粘附位点排列的单细胞模式阵列。在两种细胞衍生模式下培养的细胞均显示出一种由其形态,黏附状态,细胞骨架组织和核特性(定义了模式的COI概括)所定义的细胞结构。此外,对图案设计的略微修改允许抑制特定的肌动蛋白应力纤维并直接调节粘附部位的动力学。这种图案化方法提供了一种策略,可产生更均一的细胞群,消除细胞骨架结构,粘附动力学和细胞内张力对机械转导介导的过程的影响,并提供用于高通量细胞测定的平台。

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