Ku, T. et al. Nat. Biotechnol. http://dx.doi.org/10.1038/nbt.3641 (2016).

Tillberg, P.W. et al. Nat. Biotechnol. http://dx.doi.org/10.1038/nbt.3625 (2016).

Expansion microscopy (ExM) is a super-resolution imaging technique in which scientists anchor labels to targets of interest within a sample and then increase the size of that sample using a swellable gel. This swelling allows subdiffraction-limited structures to be imaged with conventional microscopes. One drawback of ExM is that native proteins are digested by proteases prior to expansion and therefore cannot be probed directly. Papers from two groups describe improvements to ExM that bypass this limitation. Tillberg et al. developed protein retention ExM (proExM), in which proteins, rather than labels, are cross-linked to the gel for expansion. Ku et al. developed magnified analysis of the proteome (MAP), a method that prevents protein cross-linking and denatures proteins prior to expansion, preserving protein content. Both methods now allow users to label with conventionally labeled antibodies and endogenous fluorescent proteins, broadening the utility of ExM.