Mechanical tension in axonal development (and regeneration?)
Evidence is presented that mechanical tension underlies all four phases of axonal development: (1) initiation, including axon/dendrite specification; (2) growth-cone-mediated elongation; (3) towed/stretch growth after the growth cone has reached its target; and (4) axonal retraction. Tension is experimentally applied to axons of cultured neurons with force-calibrated micro-needles. Elongation rate is shown to be directly proportional to the magnitude of tension. That is, the relationship between elongation rate and tension resembles a dashpot, arguing for very direct control of mass addition by tension. Further, elongation rates from applied tension far exceed those of growth cone-mediated elongation. These quantitative results have been obtained from several types of cultured neurons from both the central and peripheral nervous systems. An important extension of this work would be to apply tension-stimulated/controlled axonal elongation to the problem of nerve regeneration/repair, particularly for sensory and motor neurons. Much current thinking focuses on the use of magnetic beads and magnets to apply tension. Success will require use of primary neurons; ability to apply tension through a biological matrix; trade-offs for magnet technology; and advances in magnetic bead technology.
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