Measuring the mechanical properties (i.e., elasticity in terms of Young’s modulus) of biological samples using Atomic Force Microscopy (AFM) indentation at the nanoscale has opened new horizons in studying and detecting various pathological conditions at early stages, including cancer and osteoarthritis. It is expected that AFM techniques will play a key role in the future in disease diagnosis and modeling using rigorous mathematical criteria (i.e., automated user-independent diagnosis). In this review, AFM techniques and mathematical models for determining the spatial variability of elastic properties of biological materials at the nanoscale are presented and discussed. Significant issues concerning the rationality of the elastic half-space assumption, the possibility of monitoring the depth-dependent mechanical properties, and the construction of 3D Young’s modulus maps are also presented.
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