Biology subjects

Tan, X. H. M.

Publications and source records attributed to Tan, X. H. M..

3 recordsLinked to original sources

bioRxiv2024

Label-Free Optical Mapping for Large-Area Biomechanical Dynamics of Multicellular Systems

Mapping cellular activities over large areas is crucial for understanding the collective behaviors of multicellular systems. Biomechanical properties, such as cellular traction force, serve as critical regulators of physiological states and molecular configurations. However, existing technologies for mapping large-area biomechanical dynamics are limited by the small field of view and scanning nature. To address this, we propose a novel platform that utilizes a vast number of optical diffractive elements for mapping large-area biomechanical dynamics. This platform achieves a field-of-view of 10.6 mm X 10.6 mm, a three-orders-of-magnitude improvement over traditional traction force microscopy. Transient mechanical waves generated by monolayer neonatal rat ventricular myocytes were captured with high spatiotemporal resolution (130 fps and 20 {micro}m for temporal and spatial resolution, respectively). Furthermore, its label-free nature allows for long-term observations extended to a week, with minimal disruption of cellular functions. Finally, simultaneous measurements of calcium ions concentrations and biomechanical dynamics are demonstrated.

bioengineering↗

bioRxiv2023

Massively Concurrent Sub-Cellular Traction Force Videography enabled by Single-Pixel Optical Tracers (SPOTs)

We report a large field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells mechanical traction stress into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave. One-Sentence SummaryAn optical platform for fast, concurrent measurements of cell mechanics at 83 frames per second, over a large area of 13mm2.

bioengineering↗

bioRxiv2019

β-adrenergic signaling modulates cancer cell mechanotype through a RhoA-ROCK-myosin II axis

The ability of cells to deform and generate forces are key mechanical properties that are implicated in metastasis. While various soluble and mechanical cues are known to regulate cancer cell mechanical phenotype or mechanotype, our knowledge of how cells translate external signals into changes in mechanotype is still emerging. We previously discovered that activation of {beta}-adrenergic signaling, which results from soluble stress hormone cues, causes cancer cells to be stiffer or less deformable; this stiffer mechanotype was associated with increased cell motility and invasion. Here, we characterize how {beta}-adrenergic activation is translated into changes in cellular mechanotype by identifying molecular mediators that regulate key components of mechanotype including cellular deformability, traction forces, and non-muscle myosin II (NMII) activity. Using a micropillar assay and computational modelling, we determine that {beta}AR activation increases cellular force generation by increasing the number of actin-myosin binding events; this mechanism is distinct from how cells increase force production in response to matrix stiffness, suggesting that cells regulate their mechanotype using a complementary mechanism in response to stress hormone cues. To identify the molecules that modulate cellular mechanotype with {beta}AR activation, we use a high throughput filtration platform to screen the effects of pharmacologic and genetic perturbations on {beta}AR regulation of whole cell deformability. Our results indicate that {beta}AR activation decreases cancer cell deformability and increases invasion by signaling through RhoA, ROCK, and NMII. Our findings establish {beta}AR-RhoA-ROCK-NMII as a primary signaling axis that mediates cancer cell mechanotype, which provides a foundation for future interventions to stop metastasis.

cancer biology↗