Understanding the mechanisms underpinning cellular responses to microenvironmental cues requires tight control not only of the complex milieu of soluble signaling factors, extracellular matrix (ECM) connections and cell-cell contacts within cell culture, but also of the biophysics of human cells. Advances in biomaterial fabrication technologies have recently facilitated detailed examination of cellular biophysics and revealed that constraints on cell geometry arising from the cellular microenvironment influence a wide variety of human cell behaviors. Here, we create an in vitro platform capable of precise and independent control of biochemical and biophysical microenvironmental cues by adapting microcontact printing technology into the format of standard six- to 96-well plates to create MicroContact Printed Well Plates (μCP Well Plates). Automated high-content imaging of human cells seeded on μCP Well Plates revealed tight, highly consistent control of single-cell geometry, cytoskeletal organization, and nuclear elongation. Detailed subcellular imaging of the actin cytoskeleton and chromatin within live human fibroblasts on μCP Well Plates was then used to describe a new relationship between cellular geometry and chromatin dynamics. In summary, the μCP Well Plate platform is an enabling high-content screening technology for human cell biology and cellular engineering efforts that seek to identify key biochemical and biophysical cues in the cellular microenvironment.

中文翻译：

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微图案多孔板的高内涵成像揭示了细胞几何形状和细胞骨架对染色质动力学的影响。

要了解支撑细胞对微环境线索反应的机制，不仅需要严格控制可溶性信号因子，细胞外基质（ECM）连接和细胞培养中细胞间接触的复杂环境，而且还必须严格控制人类细胞的生物物理学。生物材料制造技术的进步最近促进了对细胞生物物理学的详细检查，并揭示了由细胞微环境引起的对细胞几何形状的限制会影响多种人类细胞行为。在这里，我们通过将微接触印刷技术调整为标准的六孔至96孔板的格式以创建MicroContact印刷孔板（μCP孔板），创建了一个能够精确，独立地控制生化和生物物理微环境线索的体外平台。接种在μCP孔板上的人类细胞的自动高含量成像显示出对单细胞几何形状，细胞骨架组织和核伸长的紧密，高度一致的控制。然后，使用μCP孔板上的活人成纤维细胞内肌动蛋白细胞骨架和染色质的详细亚细胞成像来描述细胞几何形状与染色质动力学之间的新关系。总之，μCP孔板平台是一种用于人类细胞生物学和细胞工程研究的高内涵筛选技术，旨在鉴定细胞微环境中的关键生化和生物物理线索。然后，使用μCP孔板上的活人成纤维细胞内肌动蛋白细胞骨架和染色质的详细亚细胞成像来描述细胞几何形状与染色质动力学之间的新关系。总之，μCP孔板平台是一种用于人类细胞生物学和细胞工程研究的高内涵筛选技术，旨在鉴定细胞微环境中的关键生化和生物物理线索。然后，使用μCP孔板上的活人成纤维细胞内肌动蛋白细胞骨架和染色质的详细亚细胞成像来描述细胞几何形状与染色质动力学之间的新关系。总之，μCP孔板平台是一种用于人类细胞生物学和细胞工程研究的高内涵筛选技术，旨在鉴定细胞微环境中的关键生化和生物物理线索。