Turnkey video-rate atomic force microscopy for nanometre resolution imaging of functional biomolecules and cellular surfaces

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Microscopes are our windows to the cell. Their importance is illustrated by the recent awards of Nobel prizes for super-resolution fluorescence microscopy (2014) and for cryo-electron microscopy (2017). These Nobel prizes also highlight the main types of microscopy that are currently used in biology: fluorescence microscopy, which can provide information on live cells, but at relatively poor resolution (~100s of nm), and electron microscopy, which can provide high-resolution images of biological molecules and cells, but requires samples to be frozen. Using atomic force microscopy, we circumvent some of the limitations of other types of microscopy by effectively tracing the surface of a sample (biological or other) with a very sharp needle, enabling us to image functional biological molecules and living cells as ~1 nm resolution. Since we trace these samples line by line to build an entire image, this is a relatively slow type of microscopy.Here we apply for funding to purchase a so-called high-speed atomic force microscope, which incorporates multiple developments to speed image acquisition up from minutes to less than seconds per frame. We will install the equipment in a well-established user facility and anticipate wide use across different disciplines and institutions. For the short-to-medium term, first experiments we plan are related to protein-DNA interactions that determine DNA packing in the cell, commercial DNA-based nanomaterials developed to facilitate chemical reactions, reshaping of biological membranes, molecular interactions that define how living cells bind to substrates, disruption of bacterial surfaces by next-generation antibiotics, and the molecular structures that define cell shape and mechanics.