Subcellular Mechanical Imaging of Erythrocytes with Optically Correlated Scanning Ion Conductance Microscopy

We report mapping the mechanical properties of human red blood cells at submicron scales. Mapping is achieved via a new approach to scanning ion conductance microscopy correlated with optical microscopy. A three-point calibration and affine transformation are utilized to correlate pixel locations registered in optical images with pipette position, which facilitates initial targeting and subsequent tracking and analysis of red blood cells. By recording the response of pipette approach curves and sample compliance at each approach, maps of the Young's modulus of samples and pipette indentation are recorded at subcellular spatial resolution. Comparison of normal and diamide-treated red blood cells shows a significant increase in cell stiffness and a concomitant decrease in deformability, clearly demonstrating the quantitative abilities of the correlative approach taken here for stiffness measurements of intact cellular samples.