Neurofilament networks: Salt-responsive hydrogels with sidearm-dependent phase behavior

Publication date: July 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 7
Author(s): Joanna Deek, Peter J. Chung, Cyrus R. Safinya
BackgroundNeurofilaments (NFs) — the neuron-specific intermediate filament proteins — are assembled into 10nm wide filaments in a tightly controlled ratio of three different monomer types: NF-Low (NF-L), NF-Medium (NF-M), and NF-High (NF-H). Previous work on reconstituted bovine NF hydrogels has shown the dependence of network properties, including filament alignment and spacing, on the subunit composition.MethodsWe use polarized optical microscopy and SAXS to explore the full salt-dependent phase behavior of reconstituted bovine NF networks as a function of various binary and ternary subunit ratios.ResultsWe observe three salt-induced liquid crystalline phases: the liquid-ordered BG and NG phases, and the disordered IG phase. We note the emergent sidearm roles, particularly that of NF-H in driving the parallel to cross-filament transition, and the counter-role of NF-M in suppressing the IG phase.ConclusionsIn copolymers of NF-LH, NF-H shifts the IG to NG transition to nearer physiological salt concentrations, as compared to NF-M in copolymers of NF-LM. For ternary mixtures, the role of NF-H is modulated by the ratio of NF-M, where beneath 10wt.% NF-M, NF-H drives the transition to the disordered phase, and above which NF-H increases interfilament spacing.General significanceUnderstanding the role of individual subunits in regulating the network structure will enable us to understand the mechanisms that drive the dysfunction of these networks, as observed in diseased conditions.

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