Force nanoscopy of living cells

The emerging field of ‘live cell nanoscopy’ has revolutionized the way biologists explore the living cell at molecular resolution. Whereas far-field fluorescence nanoscopy enables the study of the nanoscale localization and dynamics of biomolecules in cells, recent developments in atomic force microscopy (AFM) techniques offer unprecedented opportunities for imaging the structural heterogeneity of cell surfaces, and for probing the functional properties of their molecular machineries (Figure 1). In the past few years, AFM-based force nanoscopy has enabled key breakthroughs in cell biology, including: deciphering the nanoscale architecture of cell surfaces and their remodelling upon changes to the cell's functional state; understanding cellular mechanics and their functional implications; quantifying the cell adhesion forces that contribute to processes like tissue development, cell division, and bacterial infection; unravelling the molecular elasticity of cellular proteins; and elucidating how cells reassemble membrane receptors into nanodomains and modulate their functional state. In this Primer, we explain the basic principles of AFM and provide a snapshot of some of the exciting work being done in cell biology using this multifunctional tool.