Precise localization and biophysical characterization of cellular structures is a key to the understanding of biological processes happening both inside the cell and at the cell surface. Atomic force microscopy is a powerful tool to study the cell surface – topography, elasticity, viscosity, interactions – and also the visco- elastic behavior of the underlying cytoplasm, cytoskeleton or the nucleus. Here, we demonstrate the ability of atomic force microscopy to also map and characterize organelles and microorganisms inside cells, at the nanoscale, by combining stiffness tomography with super-resolution fluorescence and elec- tron microscopy. By using this correlative approach, we could both identify and characterize intracellular compartments. The validation of this approach was performed by monitoring the stiffening effect accord- ing to the metabolic status of the mitochondria in living cells in real-time.
Sébastien Janel, Séverine Divoux, Michka Popoff, Franck Perez, Nicolas Barois, Elisabeth Werkmeister, and Frank Lafont