Cell Studies Using Dynamic and 3D Micro-Structured Platforms

Previously, cell studies have largely been performed in static and 2D conditions. However, cells in vivo are in 3D environments, and interact with the environment through chemical, physical, and topological factors. Microfabrication of 3D microstructures enabled us to create precisely engineered cell microenvironments, and obtain comprehensive information from single cells. Meanwhile, dynamic cell studies are important to decipher the cellular process in response to mechanical stimuli which naturally occur in human body such as mechanical stretch by breathing and shear stress by blood flow. My research has advanced the cell studies in two aspects. First, the innovation of a 3D micro-structured platform which could trap single cells while being compatible for versatile integrations. Combined with surface enhanced Raman spectroscopy (SERS) substrate, the mechanical trap functioned as a shell sensor which rendered the complex surface of a 3D object accessible for label-free surface chemical analysis. Furthermore, utilizing selective patterning and fluorescence labeling, the mechanical trap allowed for single cell organization and polarization studies under 3D confined space and contact force. In addition, incorporated with a helical tail, the single cell gripper could be directed as an active robotic device for microscale surgical and therapeutic tasks. Together, the system provided novel platforms for single cell manipulation and analysis. The second aspect of my work demonstrated the crucial role of the nuclear envelope protein emerin in cellular adaptation to mechanical stretch. Fetal lung fibroblasts were studied under physiologically relevant fetal breathing conditions. Results indicated that emerin could affect cell shape, cytoskeletal actin organization and cellular polarization to mechanical stretch, and it also regulated extracellular matrix fibronectin production and fibrillogenesis. The study uncovered new roles of emerin in cellular structure and function, highlighted the importance of nuclei in cellular responses to mechanical perturbations, and offered new insights on the clinical investigation of lung development and laminopathies