with Martin Kröger, Viola Vogel and Anna C. Balazs

We developed a coarse-grained model of Fibronectin fibers that captures the force-induced exposure of cryptic sites upon extension. The cryptic interactions are proven to play a key-role in enhancing mechanical toughening of the fibers. 

O. Peleg el al., Biophys. J. (2012)
I. Salib el al., Langmuir (2011) 

Featured in New and Notable: Biophys. J. 3:109, 1814-1815 (2012


Inspired by molecular mechanisms that cells exploit to sense mechanical forces and convert them into biochemical signals, chemists dream of designing mechanochemical switches integrated into materials. Using the adhesion protein fibronectin, whose multiple repeats essentially display distinct molecular recognition motifs, we derived a computational model to explain how minimalistic designs of repeats translate into the mechanical characteristics of their fibrillar assemblies. The hierarchy of repeat-unfolding within fibrils is controlled not only by their relative mechanical stabilities, as found for single molecules, but also by the strength of cryptic interactions between adjacent molecules that become activated by stretching. The force-induced exposure of cryptic sites furthermore regulates the nonlinearity of stress-strain curves, the strain at which such fibers break, and the refolding kinetics and fraction of misfolded repeats (see movie below). Gaining such computational insights at the mesoscale is important because translating protein-based concepts into novel polymer designs has proven difficult.

Movie: Mechano-regulated strengthening due to cryptic sites. O. Peleg el al., Biophys. J. (2012)