Assessing Biological Samples with Scanning Probes

Scanning probe microscopes raster-scan an atomic scale sensor across an object. The scanning transmission electron microscope (STEM) uses an electron beam focused on a few angstrom spot, and measures the electron scattering power of the irradiated column of sample matter. Not only does the STEM create dark-filed images of superb clarity, but it also delivers the mass of single protein complexes within a range of 100 kDa to 100 MDa. The STEM appears to be the tool of choice to achieve high-throughput visual proteomics of single cells. In contrast, atomically sharp tips sample the object surface in the scanning tunneling microscope as well as the atomic force microscopes (AFM). Because the AFM can be operated on samples submerged in a physiological salt solution, biomacromolecules can be observed at work. Recent experiments provided new insights into the organization of different native biological membranes, and allowed molecular interaction forces, that determine protein folds and ligand binding, to be measured.