The paper introduces a new method for genetically encoding electron microscopy (EM) contrast agents called EMcapsulins. EMcapsulins are based on self-assembling protein nanocompartments called encapsulins.
By fusing different numbers (1–3) of metallothionein domains to the inner surface of encapsulins of different sizes, the authors generated 6 classes of circular barcodes that can be differentiated in EM images. The barcoded EMcapsulins provide nanometer-scale contrast that is detectable by standard EM sample preparation and imaging techniques, without needing extra steps like substrate incubation.