Atomic Force Microscopy of Living Cells

Atomic force microscopy (AFM) is a powerful technique for analyzing the structure, properties, and interactions of living cells down to molecular resolution. Rather than using an incident beam as in optical and electron microscopies, AFM measures the tiny forces acting between a sharp tip and the sample surface. While AFM imaging provides information about the nanoscale surface architecture of living cells in real time, single-molecule force spectroscopy analyzes the localization, mechanics, and interactions of the individual cell surface constituents, thereby contributing to elucidate the molecular bases of cellular events like cell adhesion and mechanosensing. In this chapter, we describe the principles of AFM and explain relevant experimental procedures, we survey recent progress made in applying AFM to microbial cells, and we discuss two recent case studies carried out in our laboratory in which the technique could unravel the mechanical and clustering behavior of cell surface sensors and adhesion proteins.