The ability to measure dynamic structural changes within a cell under applied load is essential for developing more accurate models of cell mechanics and mechanotransduction. Atomic force microscopy is a powerful tool for evaluating cell mechanics, but the dominant applied forces and sample strains are in the vertical direction, perpendicular to the imaging plane of standard fluorescence imaging.

Researchers in the Superfine Group report on a combined sideways imaging and vertical light sheet illumination system integrated with AFM. The system enables high frame rate, low background imaging of subcellular structural dynamics in the vertical plane synchronized with AFM force data. Using their system for cell compression measurements, they correlated stiffening features in the force indentation data with onset of nuclear deformation revealed in the imaging data. In adhesion studies, they were able to correlate detailed features in the force data during adhesive release events with strain at the membrane and within the nucleus.

These demonstration experiments in cellular indentation and adhesion show the capability of the AFM – PRISM/VLS system for providing new insights into cell mechanics.