Molecular force sensors
The functions of all human cell types are regulated by diverse mechanical stimuli. While mechanical forces are known to regulate key cellular functions, such as stem cell differentiation, cell proliferation, and tissue remodeling, the molecular mechanisms mediating mechanical signaling remain poorly understood. In our work, we combine protein engineering and cell biology approaches to develop novel molecular force sensors, tools that enable the sensitive visualization of piconewton-scale forces acting on nanometer-scale proteins. Leveraging these tools and cellular model systems, we investigate the mechanisms of mechanosignaling and the pathways of force transduction in mammalian cells.
Visualizing mechanical tension in tissues
Aberrant mechanical signaling is associated with the development and progression of human diseases, including lung fibrosis and solid tumors. However, invisible mechanical signals are notoriously difficult to detect and visualize, which significantly hampers research into mechanical signaling and its dysregulation in disease. By combining AI-assisted and rational protein engineering approaches, we develop methods for visualizing mechanical signals in tissue samples, including clinical specimens and tissues from animal models.
Optical control of protein functions
Optical control of engineered proteins opens attractive possibilities in research and biomedical engineering, where high spatiotemporal resolution and non-invasive protein regulation are required. We utilize both optogenetic tools and chemical protein modification to investigate the dynamic processes governing the formation and disassembly of mammalian cell adhesion complexes. In addition to cell biology research, we develop optically activated enzymes for biomedical applications, including the controlled degradation of biomaterials and drug release.
