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Atomic Force Microscopy (AFM) has a great potential as a tool to characterizemechanical and morphological properties of living cells; these properties havebeen shown to correlate with cells' fate and patho-physiological state in viewof the development of novel early-diagnostic strategies. Although severalreports have described experimental and technical approaches for thecharacterization of cell elasticity by means of AFM, a robust and commonlyaccepted methodology is still lacking. Here we show that micrometric sphericalprobes (also known as colloidal probes) are well suited for performing acombined topographic and mechanical analysis of living cells, with spatialresolution suitable for a complete and accurate mapping of cell morphologicaland elastic properties, and superior reliability and accuracy in the mechanicalmeasurements with respect to conventional and widely used sharp AFM tips. Weaddress a number of issues concerning the nanomechanical analysis, includingthe applicability of contact mechanical models and the impact of a constrainedcontact geometry on the measured elastic modulus (the finite-thickness effect).We have tested our protocol by imaging living PC12 and MDA-MB-231 cells, inorder to demonstrate the importance of the correction of the finite-thicknesseffect and the change in cell elasticity induced by the action of acytoskeleton-targeting drug.

Nanomechanical and topographical imaging of living cells by Atomic Force Microscopy with colloidal probes