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

作者：Deek Joanna^*; Chung Peter J; Safinya Cyrus R^*

来源：Biochimica et Biophysica Acta-General Subjects, 2016, 1860(7): 1560-1569.

DOI：10.1016/j.bbagen.2016.03.018

• Neurofilament
• Network
• Liquid crystal
• Hydrogel
• Sidearm-dependent
• Salt-responsive

Background: Neurofilaments (NFs) - the neuron-specific intermediate filament proteins - are assembled into 10 nm 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.
Methods: We 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.
Results: We observe three salt-induced liquid crystalline phases: the liquid-ordered B-G and N-G phases, and the disordered I-G 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 I-G phase.
Conclusions: In copolymers of NF-LH, NF-H shifts the I-G to N-G 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 10 wt.% NF-M, NF-H drives the transition to the disordered phase, and above which NF-H increases interfilament spacing.
General significance: Understanding 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.

• 出版日期2016-7