The role of stretching in slow axonal transport.
Axonal stretching is linked to rapid rates of axonal elongation. Yet the impact of stretching on elongation and slow axonal transport is unclear. Here, we develop a mathematical model of slow axonal transport that incorporates the rate of axonal elongation, protein half-life, protein density, adhesion strength, and axonal viscosity to quantify the effects of axonal stretching. We find that under conditions where the axon (or nerve) is free of a substrate and lengthens at rapid rates (>4 mm day⁻¹), stretching can account for almost 50% of total anterograde axonal transport. These results suggest that it is possible to accelerate elongation and transport simultaneously by increasing either the axon's susceptibility to stretching or the forces that induce stretching. To our knowledge, this work is the first to incorporate the effects of stretching in a model of slow axonal transport. It has relevance to our understanding of neurite outgrowth during development and peripheral nerve regeneration after trauma, and hence to the development of treatments for spinal cord injury.
Department of Mathematics, Kettering University, Flint, Michigan, USA.
Matthew
M
O'Toole
Kyle E
KE
Miller
D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D008959:Models, Neurological; D055164:Nerve Expansion; D009416:Nerve Regeneration / Q000502:physiology; D014783:Viscosity
J Cell Biol. 1986 Jul;103(1):145-58
3522601
Methods Cell Biol. 2003;71:305-23
12884696
Dev Neurobiol. 2010 Feb 15;70(3):135-49
19950193
Exp Neurol. 2010 May;223(1):11-8
19766119
Neuron. 2009 Oct 29;64(2):165-72
19874785
J Cell Biol. 1989 Dec;109(6 Pt 1):3073-83
2592415
Nat Rev Mol Cell Biol. 2009 Oct;10(10):682-96
19773780
J Neurosci. 2009 Sep 9;29(36):11316-29
19741138
Traffic. 2006 May;7(5):490-8
16643272
Biophys J. 2010 Dec 1;99(11):3571-9
21112281
Exp Cell Res. 2008 Jun 10;314(10):1981-90
18410924
J Anat. 1948 Apr;82(Pt 1-2):110-134.1
17105043
J Cell Biol. 1991 Oct;115(2):365-79
1717484
FEBS Lett. 2006 Jun 12;580(14):3525-31
16730003
Biophys J. 2008 Apr 1;94(7):2610-20
18178646
Brain. 1985 Dec;108 ( Pt 4):897-924
4075078
J Neurosci. 2007 Mar 21;27(12):3131-8
17376974
J Cell Biol. 2006 May 8;173(3):373-81
16682527
Proc R Soc Lond B Biol Sci. 1951 Dec 31;139(894):38-58
14911813
J Neurol Neurosurg Psychiatry. 1966 Feb;29(1):40-4
5910577
J Orthop Res. 2004 May;22(3):571-7
15099637
J Neurosci. 1996 Aug 15;16(16):5095-105
8756439
J Neurosci. 2004 Sep 8;24(36):7978-83
15356212
Nat Rev Mol Cell Biol. 2000 Nov;1(2):153-6
11253369
Phys Rev Lett. 2007 Jul 6;99(1):018301
17678192
J Theor Biol. 2008 Dec 21;255(4):369-77
18845167
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12611-6
19620718
Neuroscience. 2010 Sep 29;170(1):16-21
20633607
J Cell Biol. 1996 Jun;133(5):1061-9
8655579
Dev Cell. 2008 Jul;15(1):146-62
18606148
Prog Neurobiol. 2009 Nov;89(3):231-9
19664679
Dev Neurobiol. 2008 Oct;68(12):1363-77
18698606
J Neurosci. 1998 Feb 1;18(3):821-9
9437004
Physiol Rev. 2009 Jan;89(1):193-277
19126758