An AFM Dynamic Contact Model with Finite Thickness Correction to Study Micro-Rheology of Biological Cells

One of the major sources of error in Atomic Force Microscopy based Force Spectroscopic studies is bottom substrate effect, which comes due to assumption of infinite sample thickness. In the present work, anew experimentally validated mathematical correction for finite thickness of thesample is incorporated into a dynamic indentation model. This model is an extension of Sneddon’s static indentation contact model developed for conical tip indenters by incorporating the tip geometric effects, correction to hydrodynamic drag, viscoelastic nature of the sample and its finite thickness. The new model is applied to extract the viscoelastic properties of primary mesenchymal stem cells (MSC’s) extracted from human bone marrow and HCT-116 aggressive epithelial colorectal cancer cells. The micro-rheological studies indicated the presence of profound influence of infinite thickness assumption depending upon indentation depth and sample thickness at the point of indentation. The present model nullified this error and provided a better estimate of the rheological properties. The tests were conducted over a wide frequency bandwidth (0.5 to 126 Hz) and frequency dependent material properties were analyzed using power law structural damping model. It was found that MSC’s are stiffer and less viscous in nature compared to cancer cells.