Gel-expanded to gel-condensed transition in neurofilament networks revealed by direct force measurements

Nat Mater. 2010 Jan;9(1):40-6. doi: 10.1038/nmat2566. Epub 2009 Nov 15.


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. 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. 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) approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism
  • Biophysics / methods
  • Cytoskeleton / metabolism
  • Elasticity
  • Gels / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Materials Testing
  • Multiprotein Complexes / chemistry
  • Neurofilament Proteins / chemistry*
  • Osmotic Pressure
  • Static Electricity
  • Stress, Mechanical
  • Synchrotrons
  • X-Ray Diffraction


  • Gels
  • Multiprotein Complexes
  • Neurofilament Proteins