Strain history dependence of the nonlinear stress response of fibrin and collagen networks Stefan Münstera, Louise M. Jawerth, Beverly A. Leslie, Jeffrey I. Weitz, Ben Fabry, and David A. Weitz The mechanical bulk response of the networks of stiff biopolymer fibers depends on their loading history. Little is known about how the viscoelastic behavior affects the internal structure and whether this results in a modification of the nonlinear bulk mechanics of the ECM biopolymer network. In this paper, authors perform sinusoidal, large-strain oscillations on the un-cross-linked vs. cross-linked fibrin as well as collagen networks, while continuously record changes in response. They demonstrate that dynamic evolution of the mechanical response arises from delaying the onset of the srain-stiffening response and not from weakening the underlying matrices. Using confocal microscopy they present direct evidence that this behavior results from persistent lengthening of individual fibers which stretch and buckle when the network repeatedly strained. Moreover, they show that cross-linking of both fibrin and collagen networks inhibits the shift of the non-linear material response. This suggests that the molecular origin of individual fiber lengthening is slip of monomer within the fiber. Finally, they highlight the influence of this study in understanding the working behaviour of the ECM when cancer cells invade and also in engineering novel materials which are adaptable to the external loading conditions.