title: Mechanical tension applied to substrate films specifies location of neuritogenesis and promotes major neurite growth at the expense of minor neurite development.
abstract: One obstacle in neural repair is facilitating axon growth long enough to reach denervated targets. Recent studies show that axonal growth is accelerated by applying tension to bundles of neurites, and additional studies show that mechanical tension is critical to all neurite growth. However, no studies yet describe how individual neurons respond to tensile forces applied to cell bodies and neurites simultaneously; neither do any test motor neurons, a phenotype critical to neural repair. Here we examine the growth of dissociated motor neurons on stretchable substrates. E15 spinal motor neurons were cultured on poly-lactide-co-glycolide films stretched at 4.8, 9.6, or 14.3 mm day(-1). Morphological analysis revealed that substrate stretching has profound effects on developing motor neurons. Stretching increases major neurite length; it also forces neuritogenesis to occur nearest poles of the cell closest to the sources of tension. Stretching also reduces the number of neurites per neuron. These data show that substrate stretching affects neuronal morphology by specifying locations on the cell where neuritogenesis occurs and favoring major neurite growth at the expense of minor neurites. These results serve as a building block for development of new techniques to control and improve the growth of neurons for nerve repair purposes.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.|School of Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Zhang-Qi
authors.initials: ZQ
authors.lastname: Feng
authors.affiliation: Geriatrics Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare Center, Ann Arbor, Michigan.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Franz
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.|Geriatrics Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare Center, Ann Arbor, Michigan.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Leach
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.|Geriatrics Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare Center, Ann Arbor, Michigan.
authors.forename: Frank
authors.initials: F
authors.lastname: Winterroth
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.|Geriatrics Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare Center, Ann Arbor, Michigan.
authors.forename: Christina M
authors.initials: CM
authors.lastname: White
authors.affiliation: Geriatrics Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare Center, Ann Arbor, Michigan.
authors.forename: Arjun
authors.initials: A
authors.lastname: Rastogi
authors.affiliation: School of Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Gu
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.|Geriatrics Research, Education, and Clinical Center, Veterans Affairs Ann Arbor Healthcare Center, Ann Arbor, Michigan.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Corey
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002478:Cells, Cultured; D019344:Lactic Acid / Q000737:chemistry*; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D055495:Neurogenesis; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: cells; cultured; mechanical tension; motor neuron; neuritogenesis; stretch-growth