Coiled coils (CCs) are highly abundant motifs in structural proteins. Consisting of two (or more) α-helices wound around each other in a superhelical fashion, they represent essential structural elements of the cytoskeleton and the extracellular matrix (ECM). Synthetic CCs are further used as dynamo-mechanical supramolecular crosslinks in biomimetic hydrogels. Considering their function as mechanical building blocks, surprisingly little is known about the structural determinants that define the molecular mechanical properties of CCs and how these affect the linear and non-linear mechanical properties of CC-based self-assembled materials.
Using atomic force microscope-based single-molecule force spectroscopy, we have established the sequence-structure-MECHANICS relationship of a series of synthetic CCs. We show that CC mechanical stability depends on coiled coil length, helix propensity and hydrophobic core packing as well as on the pulling geometry. Based on this knowledge, we have developed a library of CCs with tuneable mechanical properties and synthesized a series of poly(ethylene glycol)-based hydrogels using these CCs as dynamic crosslinks. The resulting hydrogels consist entirely of mechanically characterized molecular building blocks and allow for establishing a direct relationship between molecular and bulk mechanics. Once equipped with a fluorescence reporter system, the CCs are intended to self-report on their mechanical state and allow for visualizing crosslink rupture in real time. This will not only provide unprecedented insights into material failure mechanisms, but also yield a smart ECM mimic for investigating the molecular forces involved in cellular mechanosensing.