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 forces, serve as critical regulators of physiological states and molecular configurations. However, existing technologies for mapping large-area biomechanical dynamics, which arise from changes in cellular traction forces, are limited by their small field of view and scanning-based nature. To address these limitations, we propose a novel platform that utilizes a vast number of optical diffractive elements to profile large-area biomechanical dynamics. This platform achieves a field of view of 10.6 mm × 10.6 mm, a three-order-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 μm for temporal and spatial resolution, respectively). Furthermore, its label-free nature allows for long-term observations extended to a week, with minimal disruption to cellular functions. Finally, simultaneous measurements of calcium ion concentrations and biomechanical dynamics are demonstrated.