Abstract
Mechanical tension is a robust regulator of axonal development of cultured neurons. We review work from our laboratory, using calibrated glass needles to measure or apply tension to chick sensory neurons, chick forebrain neurons, and rat PC12 cells. We survey direct evidence for two different regimes of tension effects on neurons, a fluid-like growth regime, and a nongrowth, elastic regime. Above a minimum tension threshold, we observe growth effects of tension regulating four phases of axonal development:
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1.
Initiation of process outgrowth from the cell body;
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2.
Growth cone-mediated elongation of the axon;
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3.
Elongation of the axon after synaptogenesis, which normally accommodates the skeletal growth of vertebrates; and
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4.
Axonal elimination by retraction.
Significantly, the quantitative relationship between the force and the growth response is suprisingly similar to the simple relationship characteristic of Newtonian fluid mechanical elements: elongation rate is directly proportional to tension (above the threshold), and this robust linear relationship extends from physiological growth rates to far-above-physiological rates. Thus, tension apparently integrates the complex biochemistry of axonal elongation, including cytoskeletal and membrane dynamics, to produce a simple “force input/growth output” relationship. In addition to this fluid-like growth response, peripheral neurons show elastic behaviors at low tensions (below the threshold tension for growth), as do most cell types. Thus, neurites could exert small static forces without diminution for long periods. In addition, axons of peripheral neurons can actively generate modest tensions, presumably similar to muscle contraction, at tensions near zero. The elastic and force-generating capability of neural axons has recently been proposed to play a major role in the morphogenesis of the brain.
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Heidemann, S.R., Lamoureux, P. & Buxbaum, R.E. Cytomechanics of axonal development. Cell Biochem Biophys 27, 135–155 (1997). https://doi.org/10.1007/BF02738107
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DOI: https://doi.org/10.1007/BF02738107