After the revolution: how is Cryo-EM contributing to muscle research?

The technique of electron microscopy (EM) has been fundamental to muscle research since the days of Huxley and Hanson. Direct observation of how proteins in the sarcomere are arranged and visualising the changes that occur upon activation have greatly increased our understanding of function. In the 1980s specimen preparation techniques for biological EM moved away from traditional fixing and staining. The technique known as cryo-electron microscopy (Cryo-EM) was developed, which involves rapidly freezing proteins in liquid ethane which maintains them in a near native state. Within the last 5 years there has been a step change in the achievable resolution using Cryo-EM. This 'resolution revolution' can be attributed to advances in detector technology, microscope automation and maximum likelihood image processing. In this article we look at how Cryo-EM has contributed to the field of muscle research in this post revolution era, focussing on recently published high resolution structures of sarcomeric proteins.