We show that the nonlinear mechanical response of networks formed from un-cross-linked fibrin or collagen type I continually changes in response to repeated large-strain loading. We demonstrate that this dynamic evolution of the mechanical response arises from a shift of a characteristic nonlinear stress-strain relationship to higher strains. Therefore, the imposed loading does not weaken the underlying matrices but instead delays the occurrence of the strain stiffening. Using confocal microscopy, we present direct evidence that this behavior results from persistent lengthening of individual fibers caused by an interplay between fiber stretching and fiber buckling when the networks are repeatedly strained. Moreover, we show that covalent cross-linking of fibrin or collagen inhibits the shift of the nonlinear material response, suggesting that the molecular origin of individual fiber lengthening may be slip of monomers within the fibers. Thus, a fibrous architecture in combination with constituents that exhibit internal plasticity creates a material whose mechanical response adapts to external loading conditions. This design principle may be useful to engineer novel materials with this capability.ECM | nonlinear rheology | factor XIII | blood clot N etworks of stiff biopolymer fibers are a major component of the structural architecture of multicellular organisms; their unique material properties provide rigidity and protect structural integrity. These networks are particularly important in the extracellular matrix (ECM) where they provide mechanical support to living cells and form many of the load-carrying structures in the body. One important example is fibrin, which forms the underlying scaffold of blood clots and the provisional matrix (1). Another important example is collagen type I, the major structural constituent of all connective tissue, tendons, ligaments, and bone (2). Because the in vivo structure of these fiber networks is so complex, investigations of in vitro networks of both proteins have been used to explore their structure and unique mechanical properties, and to elucidate their underlying design principles. Interestingly, fibrin and collagen exhibit many similar features: Both proteins self-assemble into thick, hierarchically ordered, rather stiff fibers through electrostatic and hydrophobic interactions (3, 4); these fibers associate into sparse, 3D networks that possess unusual mechanical properties not seen in synthetic polymers. In both cases, these networks display highly nonlinear mechanics and stiffen significantly as the strain increases (5-8). In addition, they are both also viscoelastic: They partially store elastic energy and partially relax internal stress through dissipative processes (9-12). All of these properties are delicately influenced by the structure of the networks, by the molecular interactions between monomers, and by the addition of covalent cross-links (7,13,14). This creates a delicate interplay between the viscoelastic and nonlinear mechanical properties of these ne...