Mechanical Mapping of Thin Elastic Films and Living Cells With Spherical Tip Atomic Force Microscopy Probes at Large Indentations

An explicit semi‐analytical model to quantify large indentation force curves acquired on elastic thin films and living cells on rigid substrates with spherical tip Atomic Force Microscopy (AFM) probes is presented. The model accounts for the bottom effect in the whole indentation range and overcomes the limitations of Sneddon's and Hertz's contact models, which are valid for semi‐infinite thick samples, and of paraboloid tip models with bottom effect correction (BEC) that are applicable to spherical tips only for relatively small indentations. The model is experimentally validated with force volume measurements on polyacrylamide (PAA) hydrogel thin films, where excellent agreement is obtained. The accurate correction of the bottom effect demonstrates that the intrinsic Young's modulus of PAA thin films increases for thickness below a critical value (∼15 µm). The model also shows excellent agreement with force curves acquired on live macrophages, providing accurate Young's modulus values for these very soft cells ( E ∼200 Pa). Young's modulus values extracted with the proposed model significantly differ from those obtained from Sneddon's or paraboloid models with BEC, whose values deviate by 100% and −25%, respectively. The generalization of the model to non‐rigid substrates as well as its validity against non‐linear effects are also discussed.