Subsurface Imaging of Cell Organelles by Force Microscopy

The development of high-resolution, label-free, noninvasive, and subsurface microscopy methods of living cells remains a formidable problem. Force-microscopy-based stiffness measurements contribute to our understanding of single-cell nanomechanics. The elastic properties of the cell’s outer structures, such as the plasma membrane and actin cytoskeleton, dominate stiffness measurements, which in turns prevents the imaging of intracellular structures. We propose that the above limitation could be overcome by combining 2D sections of the cell’s viscoelastic properties. We show the simultaneous imaging of the outer cell’s cytoskeleton and the organelles inside the nucleus. The elastic component of interaction force carries information on the cell’s outer elements as the cortex and the actin cytoskeleton. The inelastic component is sensitive to the hydrodynamic drag of the inner structures such the nucleoli.