High-strain mechanics of fibrin gels. (Top) Increasing levels of shear strain (bar) induce a sequence of distinct elastic regimes. (Bottom) Typical stress-stiffening behavior of a fibrin gel (9 μM). The color coding of the background indicates the transition from a regime dominated by entropic elasticity at the network level (red) to a regime dominated by entropic elasticity at the fiber level (green). The initial, linear network stiffness reflects thermal fluctuations of the fibers (regime 1). Strains of a few percent pull out the thermal slack from fiber segments between cross links, leading to network stiffening (regime 2). Even larger strains cause fiber stretching, resulting in a second linear regime (regime 3). The elastic modulus would remain constant for fibers with a linear stretch modulus (dashed line). Instead, the modulus increases again (regime 4), indicating stretching of flexible regions within the fibers. The increase is consistent with the σ3/2 response expected for wormlike chains (dashed line). Forced-unfolding of fibrin monomers may start before network rupture (regime 5).