Cationic liposome–microtubule complexes: Pathways to the formation of two-state lipid–protein nanotubes with open or closed ends

Raviv, Uri; Needleman, Daniel; Li, Youli; Miller, Herbert C.; Wilson, Leslie; Safinya, Cyrus R.

doi:10.1073/pnas.0502183102

Cited by 95 publications

(108 citation statements)

References 41 publications

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“…2D, bottom profile) (0-0.46 wt% of 20k PEO), where DIC shows the N MT phase, fits of background-subtracted scattering corresponded to a hollow cylinder form factor, with inner radii (∼8 nm) and cylinder thickness (4.9 nm) consistent with EM data of MTs (42). This behavior is similar to previous reports of bare MTs, where SAXS profiles of the N MT phase shows no evidence of a correlation peak (5,32,40,41,43,44). At intermediate osmotic pressures (∼1-3 wt% of 20k PEO), where DIC shows bundled MTs (Fig.…”

Section: Resultssupporting

confidence: 77%

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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Section: Resultssupporting

confidence: 77%

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 sequence of events outlined above leads to a strong electrostatic attraction. This type of electrostatic interaction has been observed for self-assembled complexes between membranes and a variety of anionic polymers, including DNA [64][65][66], F-actin [67], microtubules [68], and filamentous phages [69].…”

Section: Electrostaticsmentioning

confidence: 76%

Arginine‐rich cell‐penetrating peptides

et al. 2009

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a b s t r a c tArginine-rich cell-penetrating peptides are short cationic peptides capable of traversing the plasma membranes of eukaryotic cells. While successful intracellular delivery of many biologically active macromolecules has been accomplished using these peptides, their mechanisms of cell entry are still under investigation. Recent dialogue has centered on a debate over the roles that direct translocation and endocytotic pathways play in internalization of cell-penetrating peptides. In this paper, we review the evidence for the broad range of proposed mechanisms, and show that each distinct process requires negative Gaussian membrane curvature as a necessary condition. Generation of negative Gaussian curvature by cell-penetrating peptides is directly related to their arginine content. We illustrate these concepts using HIV TAT as an example.

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“…Using synchrotron small-angle X-ray diffraction (SAXRD) and transmission electron microscopy (TEM), we found two novel structures (Raviv et al, 2005;Raviv et al, 2006). For low membrane charge density, we found that vesicles adsorb onto the MT and appear as 'beads on a rod' (BOR).…”

Section: à3mentioning

confidence: 99%

“…Tubulin was purified from bovine brains, concentrated to 45 mM, polymerized at 310 K and taxol-stabilized as described (Needleman et al, 2004b;Raviv et al, 2005). The cationic lipid used was dioleoyl(C 18:1 ) trimethyl ammonium propane (DOTAP).…”

Section: Methodsmentioning

confidence: 99%

Hierarchical bionanotubes formed by the self assembly of microtubules with cationic membranes or polypeptides

et al. 2007

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At present there is a surge in interest in biophysical research aimed at elucidating collective interactions between cellular proteins and associated biomolecules leading to supramolecular structures, with the ultimate goal of relating structure to function. The nerve cell cytoskeleton provides a rich example of highly ordered bundles and networks of interacting neurofilaments, microtubules and filamentous actin, where the nature of the interactions, structures and structure-function correlations remain poorly understood. We present synchrotron X-ray diffraction and electron microscopy data, in reconstituted protein systems from the bovine central nervous system, which reveal unexpected structures not predicted by current electrostatic theories. By mixing preassembled microtubules with charged membranes or polypeptides we found hierarchical bionanotubes made of microtubules coated by lipid bilayers or polypeptides, which in turn are coated with a third layer of tubulin oligomers forming rings or spirals.

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Cationic liposome–microtubule complexes: Pathways to the formation of two-state lipid–protein nanotubes with open or closed ends

Cited by 95 publications

References 41 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

Arginine‐rich cell‐penetrating peptides

Hierarchical bionanotubes formed by the self assembly of microtubules with cationic membranes or polypeptides

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