Viscoelastic Imaging of Living Cells Using a Noncontact Long-Needle Atomic Force Microscope

Imaging of surface topography and elasticity of living cells can provide new insights into the roles played by the cells’ volumetric and mechanical properties and their response to external forces in regulating the essential cellular events and functions. Atomic force microscopy (AFM) would be a natural means to this end, but is designed for operation in air and does not function well in a liquid biological environment. Here, we report a unique technique of noncontact viscoelastic imaging of live cells using AFM with a long-needle glass probe. Because only the probe tip is placed in a liquid medium near the cell surface, the AFM cantilever in air functions well under dual-frequency modulation, retaining its high-quality resonant modes. The probe tip interacts with the cell surface through a minute hydrodynamic flow in the nanometer-thin gap region between them without physical contact. Quantitative measurements of the cell height, volume, and Young’s modulus are conducted simultaneously. The experiment demonstrates that the long-needle AFM has a wide range of applications in the study of soft interface mechanics and mechanobiology.