CMMI-EPSRC: A Novel Multifunctional Platform to Study Cell and Nuclear Mechanosensing

细胞可以检测和解释机械信号，将它们转化为化学信号，影响重要的生物过程，如组织发育、再生和疾病。然而，细胞如何感知和响应机械力还不是很清楚。这个项目旨在探索细胞如何对机械信号做出反应，以及它们如何将这些信号传递给邻近的细胞，帮助我们更好地了解机械力如何塑造我们的身体。该项目将能够培训不同的研究人员群体，并使他们参与国际伙伴关系。该项目还包括努力招募更多的女性和本科生参与科学和工程，以及推广活动，分享关于生物医学设备及其在改善人类健康方面的应用的信息。机械力在许多生理过程中发挥关键作用，包括在发育过程中的组织形成和器官形成过程中的细胞黏附、迁移、增殖、分化和形态形成。然而，机械信号是如何传递到邻近细胞的，以及这种细胞间的机械转导是否会导致邻近细胞的核重组和基因表达的变化，仍然是个未知数。该项目利用微流体、三维成像和机器学习，旨在开发一个高通量的机械生物学平台，能够以高时空分辨率对单个细胞施加生理相关的机械力，并成像实时的细胞响应，以阐明细胞内和细胞间机械转导的分子机制。该平台将促进我们对细胞如何对机械刺激做出反应的理解，并有助于揭示力从细胞外围传递到细胞核和邻近细胞的分子机制。这项研究由NSF工程局-UKRI工程和物理科学研究理事会牵头机构机会(ENG-EPSRC)资助，NSF 20-510。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Cells can detect and interpret mechanical signals, turning them into chemical signals that impact important biological processes such as tissue development, regeneration, and diseases. However, how cells sense and respond to mechanical forces are not well understood. This project aims to explore how cells respond to mechanical signals and how they pass these signals to neighboring cells, helping us to better understand how mechanical forces shape our bodies. This project will enable training of a diverse group of researchers and involving them international partnerships. The project also involves efforts to recruit more women and undergraduate students to participate in science and engineering, and outreach activities to share information about biomedical devices and their use in improving human health.Mechanical forces play a critical role in many physiological processes including cell adhesion, migration, proliferation, differentiation and morphogenesis during tissue formation and organogenesis in development. However, how mechanical cues are transmitted to neighboring cells and whether such intercellular mechanotransduction leads to nuclear reorganization and changes in gene expression in adjacent cells remains elusive. Using microfluidics, 3D imaging, and machine learning, this project aims to develop a high throughput mechanobiology platform capable of applying physiologically relevant mechanical forces to single cells with high spatiotemporal resolution and imaging real-time cell response to elucidate molecular mechanisms of intra- and intercellular mechanotransduction. The platform will advance our understanding of how cells respond to mechanical stimuli and help reveal molecular mechanisms that underlie the transmission of forces from the cell periphery to the nucleus and neighboring cells.This research was funded under the NSF Directorate for Engineering - UKRI Engineering and Physical Sciences Research Council Lead Agency Opportunity (ENG-EPSRC), NSF 20-510.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.