(A) Schematic illustration of a stretched axon, showing unfolding of a crosslinking protein repeat as an underlying tension relaxation mechanism. The axon, initially with length , is stretched to . In the model, any cylindrical portion of axon contains various crosslinking proteins (shown using different colors) that experience the strain . The contour length of the crosslinker between two cytoskeletal filaments, , is variable because of repeat unfolding and re-folding. This process is represented by an energy potential with two minima. The tension, , pushes the unfolded minimum down and the folded minimum up. (B) Model calculation for a single elastic element for multiple step-strain protocol. Tension versus time (purple) shows a jump after strain increment is applied (red), followed by relaxation to a steady-state value (gray points), passed through by the equilibrium tension versus extension curve "(gray)". This relaxation coincides with progressive repeat unfolding, as represented by the change in rest length (inset). (C) Tension relaxation after a small change in applied strain is exponential, with a relaxation time, , that depends non-monotonically on the strain. The inset cartoons are to show that is largely controlled by re-folding at low strain, and by unfolding at higher strain. (D) Fitting the tension relaxation data obtained from experiments like the one shown in Figure 2B to a function that is the sum of two exponentials (Figure 5—figure supplement 2, Figure 5—figure supplement 4) reveals a long relaxation time (denoted ) with a qualitatively similar dependence on strain as with the model (C) and a short relaxation time (Figure 5—figure supplement 3). Model calculations in B and C were done using the following parameters for spectrin: nm (Stokke et al., 1986), nm (Xu et al., 2013), nm, nm, nm, and nm. We also used s-1, s-1(Scott et al., 2004) and pN.nm.