期刊
NATURE MATERIALS
卷 9, 期 1, 页码 40-46出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT2566
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资金
- NSF-MRSEC [DMR-0803103]
- DOE BES [DE-FG-02-06ER46314]
- Human Frontier Science Program organization
Neurofilaments (NF)-the principal cytoskeletal constituent of myelinated axons in vertebrates-consist of three molecular-weight subunit proteins NF-L (low), NF-M (medium) and NF-H (high), assembled to form mature filaments with protruding unstructured C-terminus side arms(1-5). Liquid-crystal gel networks of side-arm-mediated neurofilament assemblies have a key role in the mechanical stability of neuronal processes. Disruptions of the neurofilament network, owing to neurofilament over-accumulation or incorrect side-arm interactions, are a hallmark of motor-neuron diseases including amyotrophic lateral sclerosis(3-9). Using synchrotron X-ray scattering, we report on a direct measurement of forces in reconstituted neurofilament gels under osmotic pressure (P). With increasing pressure near physiological salt and average phosphorylation conditions, NF-LMH, comprising the three subunits near in vivo composition, or NF-LH gels, undergo for P > P-c approximate to 10 kPa, an abrupt non-reversible gel-expanded to gel-condensed transition. The transition indicates side-arm-mediated attractions between neurofilaments consistent with an electrostatic model of interpenetrating chains. In contrast, NF-LM gels remain in a collapsed state for P < P-c and transition to the gel-condensed state at P > P-c. These findings, which delineate the distinct roles of NF-M and NF-H in regulating neurofilament interactions, shed light on possible mechanisms for disruptions of optimal mechanical network properties.
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