biostudies-literatureNg SPNCI NIH HHSWellcome Trust9633-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC1887552biostudies-literatureUnknown104(23)The extracellular matrix proteins tenascin and fibronectin experience significant mechanical forces in vivo. Both contain a number of tandem repeating homologous fibronectin type III (fnIII) domains, and atomic force microscopy experiments have demonstrated that the mechanical strength of these domains can vary significantly. Previous work has shown that mutations in the core of an fnIII domain from human tenascin (TNfn3) reduce the unfolding force of that domain significantly: The composition of the core is apparently crucial to the mechanical stability of these proteins. Based on these results, we have used rational redesign to increase the mechanical stability of the 10th fnIII domain of human fibronectin, FNfn10, which is directly involved in integrin binding. The hydrophobic core of FProceedings of the National Academy of Sciences of the United States of AmericaDesigning an extracellular matrix protein with enhanced mechanical stability.PMC1887552CA47056064417R37 CA047056R01 CA047056Ohashi TClarke JBest RBRandles LGBillings KSAllen MDNg SPErickson HPfalseDesigning an extracellular matrix protein with enhanced mechanical stability.The extracellular matrix proteins tenascin and fibronectin experience significant mechanical forces in vivo. Both contain a number of tandem repeating homologous fibronectin type III (fnIII) domains, and atomic force microscopy experiments have demonstrated that the mechanical strength of these domains can vary significantly. Previous work has shown that mutations in the core of an fnIII domain from human tenascin (TNfn3) reduce the unfolding force of that domain significantly: The composition of the core is apparently crucial to the mechanical stability of these proteins. Based on these results, we have used rational redesign to increase the mechanical stability of the 10th fnIII domain of human fibronectin, FNfn10, which is directly involved in integrin binding. The hydrophobic core of F2007-01-01T00:00:00Z2007 Jun2026-05-04T17:05:52.051Z2019-03-27T02:04:05ZS-EPMC18875521753592110.1073/pnas.0609901104