title: Fibers with integrated mechanochemical switches: minimalistic design principles derived from fibronectin.
abstract: 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. Gaining such computational insights at the mesoscale is important because translating protein-based concepts into novel polymer designs has proven difficult.
authors.affiliation: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
authors.forename: Orit
authors.initials: O
authors.lastname: Peleg
authors.forename: Thierry
authors.initials: T
authors.lastname: Savin
authors.forename: German V
authors.initials: GV
authors.lastname: Kolmakov
authors.forename: Isaac G
authors.initials: IG
authors.lastname: Salib
authors.forename: Anna C
authors.initials: AC
authors.lastname: Balazs
authors.forename: Martin
authors.initials: M
authors.lastname: Kröger
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001696:Biomechanical Phenomena; D005353:Fibronectins / Q000737:chemistry*; D020894:Microfibrils / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011108:Polymers; D017510:Protein Folding; D020449:Repetitive Sequences, Amino Acid
chemical_list: D005353:Fibronectins; D011108:Polymers