Scanning Ion Conductance Microscopy of Soft Biological Matter 
Yuri Korchev
Imperial College London, Division of Medicine,
London W12 0NN, UK

Molecular Biology has advanced we know much about the individual molecular components that make up living cells down to the level of the individual atoms. The challenge, however, is to fully understand the functional integration of these components. This requires determining how the molecular machines that make up a living cell are organized and interact together not at the atomic length scale but on a nm scale. To do this we need to develop and applying nanoscale techniques for the visualization and quantification of cell machinery in real-time and on living cells. This will lead to detailed, quantitative models of sub-cellular structures and molecular complexes under different conditions for both normal and diseased cells.
This approach ultimately requires the development of novel biophysical methods. We have recently pioneered the development of an array of new and powerful biophysical tools based on Scanning Ion Conductance Microscopy [1, 2] that allow quantitative measurements and non-invasive functional imaging of single protein molecules in living cells [3]. Scanning ion conductance microscopy and a battery of associated innovative methods are unique among current imaging techniques, not only in spatial resolution of living and functioning cells fig. 2 [4], but also in the rich combination of imaging with other functional and dynamical interrogation methods (e.g electrophysiological recording from presynaptic boutons [5]). These methods, crucially, will facilitate the study of integrated nano-behaviour in living cells in health and disease.
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[4] P. Novak et al., Nat. Methods 6, 279 (2009).
[5] P Novak, et al., Neuron, 79, 1067 (2013)