A chemomechanical bifurcation landscape unifies sustained growth, length homeostasis, and regenerative collapse in axons

Axonal growth machinery is largely shared across neurons, but axons exhibit strikingly different fates depending on developmental and environmental context: sustained elongation in peripheral neurons under permissive conditions, length homeostasis in cortical neurons after target innervation, and pathological collapse into dystrophic endbulbs in injured adult central nervous system (CNS) axons. These divergent outcomes have resisted explanation by length-sensing and biomechanical models that treat long-range transport and local force generation as separate problems. We unify these phenomena through a mechanochemical model that couples bidirectional motor transport and intracellular signaling to growth-cone balance of axonal tension, actomyosin contraction, and adhesion within a single feedback loop: The lengthening axon uses its own growing transport delay to establish self-limiting mechanical feedback, as the accumulating delay reshapes signaling waveforms to progressively elevate myosin contractility against actin-driven protrusion. Two physical parameters, the transport delay and the signaling feedback strength, organize axon fate into a unified state-space landscape spanning sustained growth, length homeostasis, and pathological collapse. Reduced feedback strength weakens this self-limiting mechanical feedback by simultaneously enhancing protrusion and suppressing contractility, providing a mechanistic interpretation of axon lengthening under partial reduction of retrograde transport. Bistability in the inhibitory regime explains why mature CNS tracts persist where nascent sprouts collapse, recasting regenerative failure as a state-dependent gate rather than a capacity limit. The framework predicts that partial rather than complete inhibition of retrograde transport could shift collapsed axons across the bifurcation into a growth-permissive regime, identifying a class of interventions complementary to existing capacity-restoration strategies for nerve injury.