Many of a biological cell’s most important activities are orchestrated by collections of proteins that form macromolecular complexes, but studying these protein powwows is far from simple. Now researchers, led by Taekjip Ha, a biophysicist at the University of Illinois, Urbana-Champaign, have developed a new way to capture these complexes for detailed study. Referred to as single-molecule pull-down (SiMPull), the method relies on capturing a “prey” protein from the complex via an antibody, and then pulling the protein and all of its binding cohorts out of a cell or tissue extract and depositing the analytes on a surface, where the assembly can be studied with single-molecule fluorescence microscopy (Nature, DOI: 10.1038/nature10016). Unlike its competitor, the long-standing western blot method, SiMPull can be performed in 30 minutes rather than several hours, it does not require any preparatory purification steps, and further biochemical studies on the proteins can be undertaken after the extraction step. In addition, the technique can isolate very low abundance protein complexes and can sometimes provide quantitative information about the numbers of unique proteins in the complex.