Our latest paper together with Christian Soeller’s group is now available with open access. In this paper, we utilise the recently-described DNA-PAINT technique to achieve optical resolutions of ~10 nm as a clear improvement over the more widely used dSTORM super-resolution technique. With the improved resolution, we were able to visualise and ‘count’ individual proteins which are clustered tightly within intracellular signalling nanodomains in muscle cells of the heart. From this analysis, we learned that the giant ryanodine receptor calcium release channels are organise more loosely and heterogeneously than previously thought. It also appeared that from cluster to cluster, their calcium release properties may be regulated more differentially by varying degrees of co-clustering with regulatory protein junctophilin-2. The study itself was also a demonstration that the enhanced resolution and the new protein ‘counting’ tools are promising new tools for studying molecular-scale biophysics in excitable cells.
The picture above illustrates, with correlative image, the remarkable improvements made by the recent dSTORM and DNA-PAINT techniques over traditional optical microscopy methods like TIRF which were state-of-the-art only ~ 13 years ago.