UC Berkeley

Cellular mechanotransduction, the tight coupling between biochemical and mechanical properties of the cytoskeleton and nucleus, drives a large range of cellular processes including cell mobility, cytokinesis, vesicle transportation, or even cell fate determination affected by alterations in gene expression. In this study, we study cellular mechanotransduction by direct imaging of the actin cytoskeleton and component of nucleoskeleton during normal cellular processes and under different stresses.

A novel class of cell permeable actin filament free barbed end dye was developed to achieve high spatial and temporal resolution of actin dynamic imaging. the generation of free barbed ends of actin filaments during lamellipodia protrusion, cytokinesis and endocytosis were monitored in this study, providing new insights on the regulation of free barbed end of actin filaments during these actin-driven processes. By distinguished visualization of the filaments and barbed end pool of actin in cells, the controversial views of whether new actin polymerization is involved during cleavage furrow closure and scission were resolved, we show that there is a surge of new actin polymerization during telophase, beginning with ingression of the contractile ring and ending with the separation of daughter cells, supporting the view that new actin polymerization is involved in cytokinesis.

we further developed a triple labeling system with the genetically encoded florescent protein (FP) fused with nuclear component including emerin, Sun1, Sun2 and lamin A. The FP was carefully choosing so the excitation and emission spectrums of FP and (Si)TMR actin dyes are far apart enough to allow spontaneous imaging of the three components. Several chemicals were applied to disrupt cytoskeleton of the cells, the corresponding responses of the nucleus components were visualized real-time, providing insights on the interaction between nucleus and cytoskeleton.

we also developed a label-free optical biosensor that employs a silicon-based high-contrast grating (HCG) resonator with a spectral linewidth of ~500pm sensitive to ligand-induced changes in surface properties in collaboration with Professor Constance Chang-Hasnain’s group. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100pg/ml within 4-minutes, which is much faster than and as sensitive as current enzyme-linked immuno-assays for cTnI.