Living cell study at the single-molecule and single-cell levels by atomic force microscopy

Atomic force microscopy (AFM) has been emerging as a multifunctional molecular tool in nanobiology and nanomedicine. This review summarizes the recent advances in AFM study of living mammalian cells at the single-molecule and single-cell levels. Besides nanoscale imaging of cell membrane structure, AFMbased force measurements on living cells are mainly discussed. These include the development and application of single-molecule force spectroscopy to investigate ligand receptor binding strength and dissociation dynamics, and the characterization of cell mechanical properties in a physiological environment. Molecular manipulation of cells by AFM to change the cellular process is also described. Living-cell AFM study offers a new approach to understand the molecular mechanisms of cell function, disease development and drug effect, as well as to develop new strategies to achieve single-cell-based diagnosis.