Unraveling protein-protein interactions in clathrin assemblies via atomic force spectroscopy

► Single molecule/particle force spectroscopy (SMFS/SPFS) is introduced. ► SMFS/SPFS is used to investigate clathrin triskelia and clathrin assemblies. ► Cooperative unfolding of clathrin alpha-helix hairpin domains is revealed. ► Force spectra of triskelia and clathrin coats provide characteristic fingerprints. ► SPFS with varying force loading rate differentiates protein-protein interactions.