Complex three-dimensional structures on cellular surfaces are often damaged during high-resolution imaging of live cells. Now, hopping probe scanning ion conductance microscopy—which uses a hopping nanopipette that 'hops' instead of 'sliding'—protects surface structures from probe-induced damage. We describe hopping mode scanning ion conductance microscopy that allows noncontact imaging of the complex three-dimensional surfaces of live cells with resolution better than 20 nm. We tested the effectiveness of this technique by imaging networks of cultured rat hippocampal neurons and mechanosensory stereocilia of mouse cochlear hair cells. The technique allowed examination of nanoscale phenomena on the surface of live cells under physiological conditions.

Nanoscale live-cell imaging using hopping probe ion conductance microscopy