Pushing the Resolution Limits of High-Speed Atomic Force Microscopy

Understanding the structural dynamics of complex molecules is vital to advancing our knowledge of materials, medicine and diseases, yet there are few techniques which can capture motions at high enough speeds or resolution to understand the underlying behaviour. High-Speed atomic force microscopy (HS-AFM) allows us to video, with sub-nanometre resolution, molecules in action at greater than 10 frames per second whilst in liquid environments. However, many important dynamics occur much faster than this, the newly developed height spectroscopy mode of AFM allows motions to be measured at 100,000 times per second. The height spectroscopy method can be applied to study the diffusion of many molecules or the structural dynamics of an individual molecule. The spatial resolution of AFM is limited the by interaction area between the tip and sample. To improve spatial resolution we have taken inspiration from super resolution microscopy methods and developed localization AFM to obtain 4 angstrom resolution on protein surfaces.

In this PhD you will learn, utilise and develop HS-AFM height spectroscopy and localization AFM techniques with the aim to push past current experimental limits to study molecules including proteins at previously inaccessible time and length scales. To perform these experiments, you will develop new algorithms and analysis methods and apply theory and computation to obtain quantitative information about kinetic behaviour at the single molecule level. You will apply these methods to answer a number of possible biophysical and biomedical questions with researchers across multiple fields including Medicine, Biology, Physics and Chemistry.