Abstract

The primary goal of optical microscopy is to visualise micro or even nanoscopic structure and dynamics. Developments over the past decades have enabled routine studies down to the single molecule level and structural observations far beyond the limits defined by the diffraction limit through the use of fluorescence as a contrast mechanism. Despite its many advantages, fluorescence detection suffers from limitations such as the need of introducing an appropriate label and a fundamentally limited photon flux. I will highlight the capabilities of an alternative approach to optical microscopy that relies on the detection of light scattering called interferometric scattering microscopy (iSCAT). I will illustrate how the unique combination of nm precision and microsecond time resolution can be used to address fundamental questions about the processivity of molecular motors or the diffusion of receptors on living cells. In addition, I will show how iSCAT can detect, image and track the motion of single proteins without the need for any labels and how this sensitivity can be used to study phenomena ranging from lipid nanodomains in model membranes to micelle and vesicle dynamics relevant to pre-biotic chemistry and the origin of life.