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.
Full Text
The Full Text of this article is available as a PDF (1.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baas P. W., Heidemann S. R. Microtubule reassembly from nucleating fragments during the regrowth of amputated neurites. J Cell Biol. 1986 Sep;103(3):917–927. doi: 10.1083/jcb.103.3.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bixby J. L. Ultrastructural observations on synapse elimination in neonatal rabbit skeletal muscle. J Neurocytol. 1981 Feb;10(1):81–100. doi: 10.1007/BF01181746. [DOI] [PubMed] [Google Scholar]
- Bray D. Axonal growth in response to experimentally applied mechanical tension. Dev Biol. 1984 Apr;102(2):379–389. doi: 10.1016/0012-1606(84)90202-1. [DOI] [PubMed] [Google Scholar]
- Bridgman P. C., Dailey M. E. The organization of myosin and actin in rapid frozen nerve growth cones. J Cell Biol. 1989 Jan;108(1):95–109. doi: 10.1083/jcb.108.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buxbaum R. E., Heidemann S. R. A thermodynamic model for force integration and microtubule assembly during axonal elongation. J Theor Biol. 1988 Oct 7;134(3):379–390. doi: 10.1016/s0022-5193(88)80068-7. [DOI] [PubMed] [Google Scholar]
- Campenot R. B. The regulation of nerve fiber length by intercalated elongation and retraction. Brain Res. 1985 May;352(1):149–154. doi: 10.1016/0165-3806(85)90099-9. [DOI] [PubMed] [Google Scholar]
- Cowan W. M., Fawcett J. W., O'Leary D. D., Stanfield B. B. Regressive events in neurogenesis. Science. 1984 Sep 21;225(4668):1258–1265. doi: 10.1126/science.6474175. [DOI] [PubMed] [Google Scholar]
- Dennerll T. J., Joshi H. C., Steel V. L., Buxbaum R. E., Heidemann S. R. Tension and compression in the cytoskeleton of PC-12 neurites. II: Quantitative measurements. J Cell Biol. 1988 Aug;107(2):665–674. doi: 10.1083/jcb.107.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- George E. B., Schneider B. F., Lasek R. J., Katz M. J. Axonal shortening and the mechanisms of axonal motility. Cell Motil Cytoskeleton. 1988;9(1):48–59. doi: 10.1002/cm.970090106. [DOI] [PubMed] [Google Scholar]
- HIRAMOTO Y. MECHANICAL PROPERTIES OF SEA URCHIN EGGS. I. SURFACE FORCE AND ELASTIC MODULUS OF THE CELL MEMBRANE. Exp Cell Res. 1963 Oct;32:59–75. doi: 10.1016/0014-4827(63)90069-7. [DOI] [PubMed] [Google Scholar]
- Heidemann S. R., Joshi H. C., Schechter A., Fletcher J. R., Bothwell M. Synergistic effects of cyclic AMP and nerve growth factor on neurite outgrowth and microtubule stability of PC12 cells. J Cell Biol. 1985 Mar;100(3):916–927. doi: 10.1083/jcb.100.3.916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hiramoto Y. Rheological properties of sea urchin eggs. Biorheology. 1970 Jan;6(3):201–234. doi: 10.3233/bir-1970-6306. [DOI] [PubMed] [Google Scholar]
- Hirokawa N. Cross-linker system between neurofilaments, microtubules, and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method. J Cell Biol. 1982 Jul;94(1):129–142. doi: 10.1083/jcb.94.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobs J. R., Stevens J. K. Changes in the organization of the neuritic cytoskeleton during nerve growth factor-activated differentiation of PC12 cells: a serial electron microscopic study of the development and control of neurite shape. J Cell Biol. 1986 Sep;103(3):895–906. doi: 10.1083/jcb.103.3.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Joshi H. C., Chu D., Buxbaum R. E., Heidemann S. R. Tension and compression in the cytoskeleton of PC 12 neurites. J Cell Biol. 1985 Sep;101(3):697–705. doi: 10.1083/jcb.101.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korneliussen H., Jansen J. K. Morphological aspects of the elimination of polyneuronal innervation of skeletal muscle fibres in newborn rats. J Neurocytol. 1976 Oct;5(8):591–604. doi: 10.1007/BF01175572. [DOI] [PubMed] [Google Scholar]
- Kuczmarski E. R., Rosenbaum J. L. Studies on the organization and localization of actin and myosin in neurons. J Cell Biol. 1979 Feb;80(2):356–371. doi: 10.1083/jcb.80.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamoureux P., Buxbaum R. E., Heidemann S. R. Direct evidence that growth cones pull. Nature. 1989 Jul 13;340(6229):159–162. doi: 10.1038/340159a0. [DOI] [PubMed] [Google Scholar]
- Letourneau P. C., Ressler A. H. Inhibition of neurite initiation and growth by taxol. J Cell Biol. 1984 Apr;98(4):1355–1362. doi: 10.1083/jcb.98.4.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luckenbill-Edds L., Van Horn C., Greene L. A. Fine structure of initial outgrowth of processes induced in a pheochromocytoma cell line (PC12) by nerve growth factor. J Neurocytol. 1979 Aug;8(4):493–511. doi: 10.1007/BF01214805. [DOI] [PubMed] [Google Scholar]
- Mitchison T., Kirschner M. Cytoskeletal dynamics and nerve growth. Neuron. 1988 Nov;1(9):761–772. doi: 10.1016/0896-6273(88)90124-9. [DOI] [PubMed] [Google Scholar]
- Morrison-Graham K. An anatomical and electrophysiological study of synapse elimination at the developing frog neuromuscular junction. Dev Biol. 1983 Oct;99(2):298–311. doi: 10.1016/0012-1606(83)90279-8. [DOI] [PubMed] [Google Scholar]
- Pasternak C., Elson E. L. Lymphocyte mechanical response triggered by cross-linking surface receptors. J Cell Biol. 1985 Mar;100(3):860–872. doi: 10.1083/jcb.100.3.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Purves D., Lichtman J. W. Elimination of synapses in the developing nervous system. Science. 1980 Oct 10;210(4466):153–157. doi: 10.1126/science.7414326. [DOI] [PubMed] [Google Scholar]
- Rich M. M., Lichtman J. W. In vivo visualization of pre- and postsynaptic changes during synapse elimination in reinnervated mouse muscle. J Neurosci. 1989 May;9(5):1781–1805. doi: 10.1523/JNEUROSCI.09-05-01781.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riley D. A. Ultrastructural evidence for axon retraction during the spontaneous elimination of polyneuronal innervation of the rat soleus muscle. J Neurocytol. 1981 Jun;10(3):425–440. doi: 10.1007/BF01262414. [DOI] [PubMed] [Google Scholar]
- Roisen F., Inczedy-Marcsek M., Hsu L., Yorke W. Myosin: immunofluorescent localization in neuronal and glial cultures. Science. 1978 Mar 31;199(4336):1445–1448. doi: 10.1126/science.343252. [DOI] [PubMed] [Google Scholar]
- Schiff P. B., Fant J., Horwitz S. B. Promotion of microtubule assembly in vitro by taxol. Nature. 1979 Feb 22;277(5698):665–667. doi: 10.1038/277665a0. [DOI] [PubMed] [Google Scholar]
- Schnapp B. J., Reese T. S. Cytoplasmic structure in rapid-frozen axons. J Cell Biol. 1982 Sep;94(3):667–669. doi: 10.1083/jcb.94.3.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw G., Bray D. Movement and extension of isolated growth cones. Exp Cell Res. 1977 Jan;104(1):55–62. doi: 10.1016/0014-4827(77)90068-4. [DOI] [PubMed] [Google Scholar]
- Sinclair G. I., Baas P. W., Heidemann S. R. Role of microtubules in the cytoplasmic compartmentation of neurons. II. Endocytosis in the growth cone and neurite shaft. Brain Res. 1988 May 31;450(1-2):60–68. doi: 10.1016/0006-8993(88)91544-2. [DOI] [PubMed] [Google Scholar]
- Wessells N. K., Johnson S. R., Nuttall R. P. Axon initiation and growth cone regeneration in cultured motor neurons. Exp Cell Res. 1978 Dec;117(2):335–345. doi: 10.1016/0014-4827(78)90147-7. [DOI] [PubMed] [Google Scholar]