The goal of this proposal is to understand the role of mechanical force (tension and compression) in the assembly and organization of the cytoskeleton underlying cell shape, motility and division. Most of the experiments are investigations of force in axons of a cultured neural cell, PC 12, in which the effect of external force on growth and shape is clear. Forces are measured through the use of calibrated glass needles by a method that also gives a value for an important mechanical property, the elastic modulus, of axons.
Specific aims of the proposal are: 1) To determine how the tension in neurites (axons) of PC 12 is manifested within the microtubules and actin filaments within the neurite. 2) To determine whether neurite tension is limited by the adhesion of the neurite to the growth surface. 3) Determine the value of the elastic modulus of PC 12 neurites and whether it depends upon microtubule assembly. 4) Investigate the growth of flaccid neurites to determine the role of tension in growth cone motility 5) Determine whether increases in compressive forces on neurite microtubules cause their disassembly and 6) Develop an objective method for assessing forces exerted by cells for which the glass needle method of force measurement is infeasible. The importance of the cytoskeleton in control of motility and cell shape suggests that the proposed work has application to understanding the development and regeneration of the nervous system, animal morphogenesis, and pathological processes such as metastasis, cell shape changes and altered growth control by tumor cells.
| Lamoureux, P; Altun-Gultekin, Z F; Lin, C et al. (1997) Rac is required for growth cone function but not neurite assembly. J Cell Sci 110 ( Pt 5):635-41 |
| Lin, C; Lamoureux, P; Buxbaum, R E et al. (1995) Osmotic dilution stimulates axonal outgrowth by making axons more sensitive to tension. J Biomech 28:1429-38 |
| Heidemann, S R; Buxbaum, R E (1994) Mechanical tension as a regulator of axonal development. Neurotoxicology 15:95-107 |
| Zheng, J; Buxbaum, R E; Heidemann, S R (1994) Measurements of growth cone adhesion to culture surfaces by micromanipulation. J Cell Biol 127:2049-60 |
| Zheng, J; Buxbaum, R E; Heidemann, S R (1993) Investigation of microtubule assembly and organization accompanying tension-induced neurite initiation. J Cell Sci 104 ( Pt 4):1239-50 |
| Lamoureux, P; Zheng, J; Buxbaum, R E et al. (1992) A cytomechanical investigation of neurite growth on different culture surfaces. J Cell Biol 118:655-61 |
| Heidemann, S R; Lamoureux, P; Buxbaum, R E (1991) On the cytomechanics and fluid dynamics of growth cone motility. J Cell Sci Suppl 15:35-44 |
| Heidemann, S R; Buxbaum, R E (1991) Growth cone motility. Curr Opin Neurobiol 1:339-45 |
| Zheng, J; Lamoureux, P; Santiago, V et al. (1991) Tensile regulation of axonal elongation and initiation. J Neurosci 11:1117-25 |
| Lamoureux, P; Steel, V L; Regal, C et al. (1990) Extracellular matrix allows PC12 neurite elongation in the absence of microtubules. J Cell Biol 110:71-9 |
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