Assembly of Biological Nanostructures: Isotropic and Liquid Crystalline Phases of Neurofilament Hydrogels

Safinya, Cyrus R.; Deek, Joanna; Beck, Roy; Jones, Jayna B.; Li, Youli

doi:10.1146/annurev-conmatphys-031214-014623

Cited by 15 publications

(14 citation statements)

References 84 publications

(109 reference statements)

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“…6H). Similar chain interpenetration behavior has been reported for protruding neurofilament side arms, which are also unstructured polyampholytes, at high osmotic pressures (68)(69)(70).…”

Section: )]supporting

confidence: 78%

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Chung

Choi

Miller

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer's. Here, we report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau isoforms by synchrotron small-angle X-ray scattering (SAXS) of MT-Tau mixtures under osmotic pressure (P). In going from bare MTs to MTs with Tau coverage near the physiological submonolayer regime (Tau/tubulin-dimer molar ratio; Φ Tau = 1/ 10), isoforms with longer N-terminal tails (NTTs) sterically stabilized MTs, preventing bundling up to P B ∼ 10,000-20,000 Pa, an order of magnitude larger than bare MTs. Tau with short NTTs showed little additional effect in suppressing the bundling pressure (P B ∼ 1,000-2,000 Pa) over the same range. Remarkably, the abrupt increase in P B observed for longer isoforms suggests a mushroom to brush transition occurring at 1/13 < Φ Tau < 1/10, which corresponds to MT-bound Tau with NTTs that are considerably more extended than SAXS data for Tau in solution indicate. Modeling of Tau-mediated MT-MT interactions supports the hypothesis that longer NTTs transition to a polyelectrolyte brush at higher coverages. Higher pressures resulted in isoform-independent irreversible bundling because the polyampholytic nature of Tau leads to short-range attractions. These findings suggest an isoform-dependent biological role for regulation by Tau, with longer isoforms conferring MT steric stabilization against aggregation either with other biomacromolecules or into tight bundles, preventing loss of function in the crowded axon environment.Tau | intrinsically disordered proteins | microtubule | SAXS | force measurement

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“…6H). Similar chain interpenetration behavior has been reported for protruding neurofilament side arms, which are also unstructured polyampholytes, at high osmotic pressures (68)(69)(70).…”

Section: )]supporting

confidence: 78%

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Chung

Choi

Miller

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The experimental characterization of cytoskeletal liquid crystal phases is a nascent field (15,23,32,33). Here we describe a liquid crystal droplet, induced by the addition of cross-links and phase separated from a dilute suspension of anisotropic particles.…”

Section: Discussionmentioning

confidence: 99%

Liquid behavior of cross-linked actin bundles

Weirich

Banerjee

Dasbiswas

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

121

124

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The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid phase of actin filaments in the presence of the physiological cross-linker, filamin. Filamin condenses short actin filaments into spindle-shaped droplets, or tactoids, with shape dynamics consistent with a continuum model of anisotropic liquids. We find that cross-linker density controls the droplet shape and deformation timescales, consistent with a variable interfacial tension and viscosity. Near the liquid-solid transition, cross-linked actin bundles show behaviors reminiscent of fluid threads, including capillary instabilities and contraction. These data reveal a liquid droplet phase of actin, demixed from the surrounding solution and dominated by interfacial tension. These results suggest a mechanism to control organization, morphology, and dynamics of the actin cytoskeleton.actin | phase separation | liquid crystal | cytoskeleton T he cellular cytoplasm is a hierarchical array of diverse, soft materials assembled from biological molecules that work in concert to support cell physiology (1). The actin cytoskeleton constitutes a spectrum of materials constructed from the semiflexible polymer actin (F-actin) that are crucial in diverse physical processes ranging from cell division and migration to tissue morphogenesis (2, 3). Cross-linking and regulatory proteins assemble actin filaments into bundles and networks with varied composition, mechanics, and physiological function (4). The mechanical properties of actin assemblies regulate force generation and transmission to dynamically control morphogenic processes from the subcellular to tissue length scales (5, 6).A mechanistic understanding of cytoplasmic mechanics is obscured by the rich complexity of in vivo cytoskeletal assemblies (7) and has been investigated via in vitro model systems (8, 9). Vastly different material properties have been accessed through varying filament length, concentration, and cross-linking. For semidilute concentrations of long actin filaments (>1 μm), the mean spacing between actin filaments, or mesh size, is much smaller than the filament length. In this case, cross-linking proteins mechanically constrain actin filaments to result in space-spanning networks that are viscoelastic gels (10). The structure of cross-linked actin networks is kinetically determined, reflecting a metastable state (11, 12) that requires motor-driven stresses for significant shape changes (13). In contrast, highly concentrated solutions of short actin filaments (<1 μm) align due to entropic effects and form equilibrium liquid crystal phases (14). Liquid crystal theory has been introduced as a framework to understand actin cortex mechanics and mitotic spindle shape (5, 15), but the existence of liquid crystal-like phases at physiological conditions is uncertain.Liquid-like phases of proteins and nucleic acids have been found within the cytoplasm and are thought to be important in subcellular...

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“…The C-terminal tails of these proteins are highly disordered and serve as entropic bristles protruding outwards the neurofilament body, providing means for the bottlebrush topology of the neurofilaments, and mediating the inter-filament interactions and controlling the neuronal cytoskeletal organization. [121][122][123] These tails of the neurofilament proteins differ from each other by their length and amino acid composition. For example human NF-L, NF-M, and NF-H proteins contain 147, 504 and 613 residues, respectively.…”

Section: 120mentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

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This article continues a series of short comments on the paradoxes and wonders of the protein intrinsic disorder phenomenon by introducing the "stability of instability" paradox. Intrinsically disordered proteins (IDPs) are characterized by the lack of stable 3D-structure, and, as a result, have an exceptional ability to sustain exposure to extremely harsh environmental conditions (an illustration of the "you cannot break what is already broken" principle). Extended IDPs are known to possess extreme thermal and acid stability and are able either to keep their functionality under these extreme conditions or to rapidly regain their functionality after returning to the normal conditions. Furthermore, sturdiness of intrinsic disorder and its capability to "ignore" harsh conditions provides some interesting and important advantages to its carriers, at the molecular (e.g., the cell wall-anchored accumulation-associated protein playing a crucial role in intercellular adhesion within the biofilm of Staphylococcus epidermidis), supramolecular (e.g., protein complexes, biologic liquid-liquid phase transitions, and proteinaceous membrane-less organelles), and organismal levels (e.g., the recently popularized case of the microscopic animals, tardigrades, or water bears, that use intrinsically disordered proteins to survive desiccation).

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Assembly of Biological Nanostructures: Isotropic and Liquid Crystalline Phases of Neurofilament Hydrogels

Cited by 15 publications

References 84 publications

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Liquid behavior of cross-linked actin bundles

Paradoxes and wonders of intrinsic disorder: Stability of instability

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