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

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.