A better understanding of molecular biophysical basics of the mechanism of mechanotransduction will bring about new methods of treatment of a wide range of disorders. It is assumed that microscopic changes in cellular mechanics could break the regulation of the molecular mechanism of mechanotransduction - the process by which cells sense mechanical signals and convert them into chemical responses. There are plenty of abnormalities arisen from alterations of mechanical properties of the matrix, e.g. enhanced cancer cell metastasis. Therefore, studying of mechanical properties of live cells is very important. Noncontact topography images can be acquired via the Scanning Ion-Conductance Microscopy (SICM), which uses an electrolytic current through a nanopipette as a measure for pipette-surface distance. There are two definitely different methods of topography mapping allowed by SICM. The first one calculates cell stiffness depending on the current drop, due to the probe approach to the cell surface. The second one uses additional hydrostatic pressure through a nanopipette while the pipette-sample separation is kept constant above the cell surface. These approaches have been validated on living cells (Human prostate adenocarcinoma). As a result, two different SICM scanning methods were compared. The first method with the pipette-tip radius of 38 nm showed 895.69 ± 195.95 Pa membrane stiffness. The second one, with the tip radius 120 nm and additional pressure from 3kPa to 6kPa, showed 887.41 ± 178.31 Pa membrane stiffness. In connection with that, these methods are comparable, and give the same mechanical properties. The biological part of research was funded by the Ministry of Education and Science of the Russian Federation implemented by a governmental decree dated 16 March 2013, no. 211, The Russian Science Foundation, grant number No 19-79-30062, funded SICM method.