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

CMMI-EPSRC：研究细胞和核机械传感的新型多功能平台

• 批准号: 2325750
• 负责人: Melikhan Tanyeri
• 金额: $ 47.94万
• 依托单位: Duquesne University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2325750&HistoricalAwards=false
• 关键词: CMMI; EPSRC; Novel; Multifunctional; Platform

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.

细胞可以检测和解释机械信号，将其转化为影响重要生物过程的化学信号，如组织发育、再生和疾病。然而，细胞是如何感知和响应机械力的，目前还不清楚。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，帮助我们更好地理解机械力如何塑造我们的身体。这个项目将能够培训一批不同的研究人员，并使他们参与国际伙伴关系。该项目还包括努力招收更多的妇女和本科生参加科学和工程，并开展外联活动，分享关于生物医学设备及其在改善人类健康方面的使用的信息。机械力在细胞粘附、迁移、增殖、分化、组织形成和器官发生等生理过程中发挥着重要作用。然而，机械信号是如何传递到邻近细胞的，以及这种细胞间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，仍然是一个谜。利用微流体、3D成像和机器学习，本项目旨在开发一个高通量的机械生物学平台，能够将生理学相关的机械力应用于单细胞，具有高时空分辨率和成像实时细胞反应，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响应机械刺激的理解，并有助于揭示细胞外周向细胞核和邻近细胞传递力的分子机制。本研究由NSF工程局- UKRI工程和物理科学研究委员会领导机构机会（ENG-EPSRC）资助，NSF 20-510。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。