OptoRheo: Simultaneous in situ micro-mechanical sensing and 3D imaging of live cell cultures

Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair to disease progression. To better understand cell-matrix interactions, we have developed an optical instrument combining light sheet fluorescence microscopy with particle tracking microrheology. We name this new instrument OptoRheo. OptoRheo lets us image cells in 3D as they proliferate over several days while simultaneously sensing the biomechanical properties of the surrounding extracellular and pericellular matrix at a sub-cellular scale. OptoRheo can be used in two operational modalities to extend the dynamic range of microrheology measurements, making the instrument suitable for different cell culture systems. We corroborated this by characterising the ECM surrounding live breast cancer cells in two distinct culture systems, 3D hydrogels and suspension culture. This cutting-edge instrument will transform the exploration of drug transport through complex cell culture matrices and optimise the design of the next-generation disease models.