α-Synuclein Sterically Stabilizes Spherical Nanoparticle-Supported Lipid Bilayers

Chung, Peter J.; Zhang, Qingteng; Hwang, Hyeondo Luke; Leong, Alessandra; Maj, P.; Szczygieł, R.; Đufresne, Eric M.; Narayanan, Suresh; Adams, Erin J.; Lee, Ka Yee C.

doi:10.1021/acsabm.8b00774

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…and affinity (apparent dissociation constant of 92 and 42 μM, respectively) to SSLBs designed to reflect the membrane charge and size limit of synaptic vesicles (50% charged lipid and 70 nm diameter, respectively). [11] Reflecting in vitro and in vivo data of the relatively dilute binding density of S, [12,13] the protein-to-outer lipid ratio for all our experiments was 1:80 (a ratio that did not disrupt the supported lipid bilayer, Figure S1). [11] To probe the force response of this steric stabilization afforded by S at this protein-to-outer lipid ratio, SAXS was used to investigate the higher order structure of S-bound SSLBs as a function of increasing polyethylene glycol, MW = 10,000 (10kPEG), an inert osmotic depletant known to induced depletion attraction between solidsupported membrane surfaces.…”

Section: Resultssupporting

confidence: 62%

“…[11] Reflecting in vitro and in vivo data of the relatively dilute binding density of S, [12,13] the protein-to-outer lipid ratio for all our experiments was 1:80 (a ratio that did not disrupt the supported lipid bilayer, Figure S1). [11] To probe the force response of this steric stabilization afforded by S at this protein-to-outer lipid ratio, SAXS was used to investigate the higher order structure of S-bound SSLBs as a function of increasing polyethylene glycol, MW = 10,000 (10kPEG), an inert osmotic depletant known to induced depletion attraction between solidsupported membrane surfaces. [14] The azimuthally averaged line shape of S-bound SSLBs revealed that at sufficient PEG concentration (C 10kPEG = 10.5 wt/vol %, corresponding to a critical osmotic pressure P C ~ 1.3 x 10 5 Pa), there was an onset of a correlation peak (q ~ 0.0092 Å -1 ) consistent with the nearest-neighbor distance between a pair of SSLBs (Figure 1).…”

Section: Resultssupporting

confidence: 62%

“…A previous study by our group used the high scattering cross-section of SSLBs to demonstrate via X-ray photon correlation spectroscopy that S dispersed SSLB aggregates, direct evidence that S sterically stabilized membrane surfaces. [11] What remained unclear was the nature of the steric stabilization, and whether the S CTD had any role in it.…”

Section: Introductionmentioning

confidence: 99%

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The C‐Terminal Domain of α‐Synuclein Confers Steric Stabilization on Synaptic Vesicle‐Like Surfaces

Chung

Hwang

Slaw

et al. 2020

Adv Materials Inter

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While -Synuclein, an intrinsically disordered protein linked to Parkinson's disease, has been shown to associate with membrane organelles, its overall cellular function remains nebulous. -Synuclein binds to membranes through its amino-terminal domain (first ~ 100 residues), but there is no This article is protected by copyright. All rights reserved. 2 consensus on the biophysical function of the carboxyl-terminal domain (last ~ 40 residues) due, in part, to its lack of strong interaction partners and persisting intrinsic disorder even when membranebound. Here, by directly applying force on -Synuclein bound to spherical nanoparticle-supported lipid bilayers (SSLBs) and tracking higher-order structural changes through small-angle X-ray scattering, we present strong evidence that -Synuclein sterically stabilizes membrane surfaces through its carboxyl-terminal domain. Full-length -Synuclein dramatically increases the critical osmotic pressure at which SSLBs cluster (P C ~ 1.3 x 10 5 Pa) compared to -Synuclein without the carboxyl-terminal domain (P C ~ 1.9 x 10 4 Pa) at physiological salt and temperature conditions. We show this clustering of -Synuclein-bound SSLBs to be reversible and sensitive to monovalent/divalent salt, both features of grafted polyelectrolyte-mediated steric stabilization. In elucidating the biophysical function of -Synuclein in the framework of polymer science, we demonstrate that the carboxyl-terminal domain can potentially utilize its persisting intrinsic disorder to functionalize membrane surfaces.

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Section: Resultssupporting

confidence: 62%

Section: Resultssupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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The C‐Terminal Domain of α‐Synuclein Confers Steric Stabilization on Synaptic Vesicle‐Like Surfaces

Chung

Hwang

Slaw

et al. 2020

Adv Materials Inter

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“…Many of these applications are summarized in recent reviews (Leheny, 2012;Shpyrko, 2014;Sinha et al, 2014;Madsen et al, 2016;Sandy et al, 2018). Partially driven by XPCS-applicable area detectors with increasingly high frame rates (Trapani et al, 2018;Zhang et al, 2020Zhang et al, , 2018Zinn et al, 2018;Pennicard et al, 2018;Redford et al, 2018;Maj et al, 2020;Allahgholi et al, 2019;Poikela et al, 2014) but also by emerging near-diffraction-limited storage rings (DLSRs) (Eriksson et al, 2014), a growing area of interest is XPCS applied to rapidly fluctuating and often weakly scattering soft materials (Vodnala et al, 2018;Mö ller et al, 2019;Chung et al, 2019;Zhang et al, 2019;Dallari et al, 2020;Nigro et al, 2020;Frenzel et al, 2019;Yavitt et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

20 µs-resolved high-throughput X-ray photon correlation spectroscopy on a 500k pixel detector enabled by data-management workflow

Zhang¹,

Đufresne²,

Nakaye³

et al. 2021

J Synchrotron Rad

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The performance of the new 52 kHz frame rate Rigaku XSPA-500k detector was characterized on beamline 8-ID-I at the Advanced Photon Source at Argonne for X-ray photon correlation spectroscopy (XPCS) applications. Due to the large data flow produced by this detector (0.2 PB of data per 24 h of continuous operation), a workflow system was deployed that uses the Advanced Photon Source data-management (DM) system and high-performance software to rapidly reduce area-detector data to multi-tau and two-time correlation functions in near real time, providing human-in-the-loop feedback to experimenters. The utility and performance of the workflow system are demonstrated via its application to a variety of small-angle XPCS measurements acquired from different detectors in different XPCS measurement modalities. The XSPA-500k detector, the software and the DM workflow system allow for the efficient acquisition and reduction of up to ∼109 area-detector data frames per day, facilitating the application of XPCS to measuring samples with weak scattering and fast dynamics.

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“…Similar to supported bilayers on a planar surface 8 , supported lipid bilayers can be formed on spherical silica nanoparticles, presenting a relatively well-behaved membrane surface separate from the silica support by a thin aqueous layer 9 . Such supported bilayers have been used as substrates in a number of nano-biological applications [10][11][12][13][14] . Here, we report the use of supported bilayers on silica nanoparticles (SLB-nanoparticles) as a substrate for influenza virus fusion.…”

mentioning

confidence: 99%

Disentangling Viral Entry Kinetics Using Lipid Bilayers Coating Silica Nanoparticles

Giraldo¹,

Kasson²

2020

Preprint

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<div> <div> <div> <p>Enveloped viruses infect cells via fusion between the viral envelope and a cellular membrane. This membrane fusion process is driven by viral proteins, but slow stochastic protein activation dominates fusion kinetics, making it challenging to probe the role of membrane mechanics in viral entry directly. We have used bilayer-coated silica nanoparticles to restrict the deformability of lipid membranes in a controllable manner. These bilayer-coated nanoparticles are then used in a single-particle fusion assay with infectious influenza virus. We observe that as we vary the free energy of membrane deformation by changing nanoparticle size, we obtain a corresponding response in fusion kinetics and apparent fusion protein stoichiometry. We thus directly measure the effect of membrane deformability on the free-energy barrier to membrane fusion by influenza, overcoming the masking effect of slow protein activation kinetics. </p> </div> </div> </div>

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α-Synuclein Sterically Stabilizes Spherical Nanoparticle-Supported Lipid Bilayers

Cited by 13 publications

References 31 publications

The C‐Terminal Domain of α‐Synuclein Confers Steric Stabilization on Synaptic Vesicle‐Like Surfaces

The C‐Terminal Domain of α‐Synuclein Confers Steric Stabilization on Synaptic Vesicle‐Like Surfaces

20 µs-resolved high-throughput X-ray photon correlation spectroscopy on a 500k pixel detector enabled by data-management workflow

Disentangling Viral Entry Kinetics Using Lipid Bilayers Coating Silica Nanoparticles

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