The cytomechanics of axonal elongation and retraction.

Abstract

Neurites of PC12 and chick dorsal root ganglion neurons behave as viscoelastic solids in response to applied forces. This passive behavior can be modeled with three mechanical elements; a relatively stiff, undamped spring in series with a Voight element composed of a less stiff spring in parallel with a dashpot. In response to applied tensions greater than 100 microdynes, PC12 cells show lengthening behavior distinct from and in addition to the passive viscoelastic response. We interpret this as "towed growth" (Bray, D. 1984. Dev. Biol. 102:379-389) because the neurites can become twice as long without obvious thinning of the neurite and because in two cases neurite tensions fell below original rest tensions, a result that cannot be obtained with passive viscoelastic elements. The rate of towed growth showed a linear dependence of growth rate with applied tensions in 8 of 12 PC12 neurites exposed to applied tension greater than 100 microdynes. Both PC12 and chick sensory neurons showed evidence of retraction when neurite tensions were suddenly diminished. This response was measured as tension recovery after slackening in chick sensory neurites. In 62% of the cases, tension recovery exceeded and sometimes doubled the preexperimental steady-state tension. Our data indicate that this response is active tension generation by the neurite shaft. We conclude that neurite length is regulated by axial tension in both elongation and retraction. Our data suggest a three-way controller: above some tension set point, the neurite is stimulated to elongate. Below some different, lower tension threshold the neurite is stimulated to retract. Between these two tension thresholds, the neurite responds passively as a viscoelastic solid.

Xenopus gastrulation without a blastocoel roof

“…The mechanisms of molecular and cellular function in morphogenesis are defined in terms of the biomechanical and geometric context of cell populations (see Hardin, 1990). Although regorous biomechanical analysis at cell-cell population level is just beginning, progress is being made with both experimental and modeling approaches (see Koehl, 1990;Dennerll et al, 1989;Adams, et al, 1990;Koehl et al, 1990;Jamney, et al, 1991;Moore, 1992;Weliky et al, 1992), and it is important that this field be developed in order to understand the mechanisms of morphogenesis at any level.…”

Towards a unified theory for morphomechanics

“…Axons can reach a metre or more in length, indicating that the elongation involves growth induced by axial tension Gilbert 2003). Using flexible needles, Dennerll et al (1989) measured the tension in axons from dorsal root ganglion neurons of chick embryos. After attaching one end of a needle to the growth cone, they lifted it from the substrate and held the axon at a relatively fixed length until the force equilibrated.…”

Gradual stretching of the proximal nerve stump induces the growth of regenerating sprouts in rats

“…Furthermore, a linear relationship existed between the growth rate and the experimentally applied tension, and the axonal growth was regulated by mechanical tension. [1][2][3][4][5] Interestingly, the result of our present study suggested that it is also possible to lengthen the regenerating sprouts of the transected proximal nerve stump by the mechanical stretching. Thus, the stimulus of mechanical stretching also induces the growth of regenerating sprouts in vivo.…”

“…In addition, it has been reported that tension applied to the growth cones of PC12 or chick DRG neurites can induces a significant neurite outgrowth. [1][2][3][4][5] In our previous studies, we lengthened the transected proximal nerve stumps by direct gradual stretching ex vivo, and the whole nerve trunk including the endoneurium and axons were lengthened simultaneously in proportion to the stretching period. Interestingly, however, in our experiment the tip of the proximal nerve stump was significantly lengthened during gradual stretching.…”