Small-angle neutron scattering characterization of monoclonal antibody conformations and interactions at high concentrations.

Abstract:

:Small-angle neutron scattering (SANS) is used to probe the solution structure of two protein therapeutics (monoclonal antibodies 1 and 2 (MAb1 and MAb2)) and their protein-protein interaction (PPI) at high concentrations. These MAbs differ by small sequence alterations in the complementarity-determining region but show very large differences in solution viscosity. The analyses of SANS patterns as a function of different solution conditions suggest that the average intramolecular structure of both MAbs in solution is not significantly altered over the studied protein concentrations and experimental conditions. Even though a strong repulsive interaction is expected for both MAbs due to their net charges and low solvent ionic strength, analysis of the SANS data shows that the effective PPI for MAb1 is dominated by a very strong attraction at small volume fraction that becomes negligible at large concentrations. The MAb1 PPI cannot be modeled simply by a spherically symmetric central forces model. It is proposed that an anisotropic attraction strongly affects the local interprotein structure and leads to an anomalously large viscosity of concentrated MAb1 solutions. Conversely, MAb2 displays a repulsive interaction potential throughout the concentration series probed and a comparatively small solution viscosity.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Yearley EJ,Zarraga IE,Shire SJ,Scherer TM,Gokarn Y,Wagner NJ,Liu Y

doi

10.1016/j.bpj.2013.06.043

subject

Has Abstract

pub_date

2013-08-06 00:00:00

pages

720-31

issue

3

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(13)00778-9

journal_volume

105

pub_type

杂志文章
  • Effects of hydrostatic pressure on bilayer phase behavior and dynamics of dilauroylphosphatidylcholine.

    abstract::Deuterium nuclear magnetic resonance spectroscopy was used to study the thermotropic phase behavior of dilauroylphosphatidylcholine (DLPC) bilayers at pressures up to 221 MPa. Pressure was found to separate the liquid crystal to gel transition from the gel to ordered crystalline phase transition. The jump in chain ord...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(96)79842-9

    authors: Bonev B,Morrow MR

    更新日期:1996-06-01 00:00:00

  • Ca2+ regulation in the near-membrane microenvironment in smooth muscle cells.

    abstract::The microenvironment between the plasma membrane and the near-membrane sarcoplasmic reticulum (SR) may play an important role in Ca(2+) regulation in smooth muscle cells. We used a three-dimensional mathematical model of Ca(2+) diffusion and regulation and experimental measurements of SR Ca(2+) uptake and the distribu...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(03)74605-0

    authors: Bazzazi H,Kargacin ME,Kargacin GJ

    更新日期:2003-09-01 00:00:00

  • Tuning the voltage-sensor motion with a single residue.

    abstract::The Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP) represents the first discovered member of enzymes regulated by a voltage-sensor domain (VSD) related to the VSD found in voltage-gated ion channels. Although the VSD operation in Ci-VSP exhibits original voltage dependence and kinetics compared to ion chann...

    journal_title:Biophysical journal

    pub_type: 信件

    doi:10.1016/j.bpj.2012.06.030

    authors: Lacroix JJ,Bezanilla F

    更新日期:2012-08-08 00:00:00

  • Molecular mechanisms determining the strength of receptor-mediated intermembrane adhesion.

    abstract::The strength of receptor-mediated cell adhesion is directly controlled by the mechanism of cohesive failure between the cell surface and underlying substrate. Unbinding can occur either at the locus of the specific bond or within the bilayer, which results in tearing the hydrophobic anchors from the membrane interior....

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(95)79990-8

    authors: Leckband D,Müller W,Schmitt FJ,Ringsdorf H

    更新日期:1995-09-01 00:00:00

  • Muscle cross-bridges bound to actin are disordered in the presence of 2,3-butanedione monoxime.

    abstract::Electron paramagnetic resonance spectroscopy was used to monitor the orientation of muscle cross-bridges attached to actin in a low force and high stiffness state that may occur before force generation in the actomyosin cycle of interactions. 2,3-butanedione monoxime (BDM) has been shown to act as an uncompetitive inh...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(95)80375-9

    authors: Zhao L,Naber N,Cooke R

    更新日期:1995-05-01 00:00:00

  • Deuterium magnetic resonance study of the gel and liquid crystalline phases of dipalmitoyl phosphatidylcholine.

    abstract::Deuterium magnetic resonance is applied to the study of the liquid crystalline and gel phases, and of the phase transition, of a multilamellar dispersion of chain perdeuterated (d62)-dipalmitoyl phosphatidylcholine/H2O. Analysis of the deuterium spectra in terms of the moments of the spectra allows one to make quantit...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(79)85222-4

    authors: Davis JH

    更新日期:1979-09-01 00:00:00

  • Comparison of the biophysical properties of racemic and d-erythro-N-acyl sphingomyelins.

    abstract::In this study stereochemically pure d-erythro-sphingomyelins (SMs) with either 16:0 or 18:1(cisDelta9) as the N-linked acyl-chain were synthesized. Our purpose was to examine the properties of these sphingomyelins and acyl-chain matched racemic (d-erythro/l-threo) sphingomyelins in model membranes. Liquid-expanded d-e...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(99)76997-3

    authors: Ramstedt B,Slotte JP

    更新日期:1999-09-01 00:00:00

  • A novel method for study of protein folding kinetics by monitoring diffusion coefficient in time domain.

    abstract::Molecular diffusion process after the photo-induced electron injection to ferric cytochrome c (Fe(III) cyt c) in guanidine hydrochloride (GdnHCl) 3.5 M buffer solution is studied by the time-resolved transient grating technique. Circular dichroism studies have revealed that Fe(III) cyt c is unfolded under this conditi...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(03)74615-3

    authors: Nada T,Terazima M

    更新日期:2003-09-01 00:00:00

  • Effects of lipid interactions on model vesicle engulfment by alveolar macrophages.

    abstract::The engulfment function of macrophages relies on complex molecular interactions involving both lipids and proteins. In particular, the clearance of apoptotic bodies (efferocytosis) is enabled by externalization on the cell target of phosphatidylserine lipids, which activate receptors on macrophages, suggesting that (l...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.12.036

    authors: Justice MJ,Petrusca DN,Rogozea AL,Williams JA,Schweitzer KS,Petrache I,Wassall SR,Petrache HI

    更新日期:2014-02-04 00:00:00

  • A computational framework for mechanical response of macromolecules: application to the salt concentration dependence of DNA bendability.

    abstract::A computational framework is presented for studying the mechanical response of macromolecules. The method combines a continuum mechanics (CM) model for the mechanical properties of the macromolecule with a continuum electrostatic (CE) treatment of solvation. The molecules are represented by their shape and key physico...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2009.01.047

    authors: Ma L,Yethiraj A,Chen X,Cui Q

    更新日期:2009-05-06 00:00:00

  • Polyunsaturated Lipids Regulate Membrane Domain Stability by Tuning Membrane Order.

    abstract::The plasma membrane (PM) serves as the functional interface between a cell and its environment, hosting extracellular signal transduction and nutrient transport among a variety of other processes. To support this extensive functionality, PMs are organized into lateral domains, including ordered, lipid-driven assemblie...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2016.03.012

    authors: Levental KR,Lorent JH,Lin X,Skinkle AD,Surma MA,Stockenbojer EA,Gorfe AA,Levental I

    更新日期:2016-04-26 00:00:00

  • Electric-Induced Reversal of Morphogenesis in Hydra.

    abstract::Morphogenesis involves the dynamic interplay of biochemical, mechanical, and electrical processes. Here, we ask to what extent can the course of morphogenesis be modulated and controlled by an external electric field? We show that at a critical amplitude, an external electric field can halt morphogenesis in Hydra rege...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2019.09.007

    authors: Braun E,Ori H

    更新日期:2019-10-15 00:00:00

  • Continuum electrostatics fails to describe ion permeation in the gramicidin channel.

    abstract::We investigate the validity of continuum electrostatics in the gramicidin A channel using a recently determined high-resolution structure. The potential and electric field acting on ions in and around the channel are computed by solving Poisson's equation. These are then used in Brownian dynamics simulations to obtain...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(02)73905-2

    authors: Edwards S,Corry B,Kuyucak S,Chung SH

    更新日期:2002-09-01 00:00:00

  • Peptides derived from apoptotic Bax and Bid reproduce the poration activity of the parent full-length proteins.

    abstract::Bax and Bid are proapoptotic proteins of the Bcl-2 family that regulate the release of apoptogenic factors from mitochondria. Although they localize constitutively in the cytoplasm, their apoptotic function is exerted at the mitochondrial outer membrane, and is related to their ability to form transbilayer pores. Here...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.058008

    authors: García-Sáez AJ,Coraiola M,Dalla Serra M,Mingarro I,Menestrina G,Salgado J

    更新日期:2005-06-01 00:00:00

  • Are DNA transcription factor proteins maxwellian demons?

    abstract::Transcription factor (TF) proteins rapidly locate unique target sites on long genomic DNA molecules--and bind to them--during gene regulation. The search mechanism is known to involve a combination of three-dimensional diffusion through the bulk of the cell and one-dimensional sliding diffusion along the DNA. It is be...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.108.129825

    authors: Hu L,Grosberg AY,Bruinsma R

    更新日期:2008-08-01 00:00:00

  • Size effects on diffusion processes within agarose gels.

    abstract::To investigate diffusion processes in agarose gel, nanoparticles with sizes in the range between 1 and 140 nm have been tested by means of fluorescence correlation spectroscopy. Understanding the diffusion properties in agarose gels is interesting, because such gels are good models for microbial biofilms and cells cyt...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(04)74325-8

    authors: Fatin-Rouge N,Starchev K,Buffle J

    更新日期:2004-05-01 00:00:00

  • The lateral distribution of pyrene-labeled sphingomyelin and glucosylceramide in phosphatidylcholine bilayers.

    abstract::The lateral distribution of N-[10(1-pyrenyl)decanoyl]-sphingomyelin (PyrSPM) and N-[10(1-pyrenyl)decanoyl]-glucocerebroside (PyrGlcCer) was studied in multilamellar vesicles of 1,2-dipalmitoyl-, 1,2-dimyristoyl-, and 1-palmitoyl-2-oleoyl-phosphatidylcholine (DPPC, DMPC, and POPC, respectively) under anaerobic conditio...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(87)83399-4

    authors: Hresko RC,Sugár IP,Barenholz Y,Thompson TE

    更新日期:1987-05-01 00:00:00

  • Contrasting factors on the kinetic path to protein complex formation diminish the effects of crowding agents.

    abstract::The crowded environment of cells poses a challenge for rapid protein-protein association. Yet, it has been established that the rates of association are similar in crowded and in dilute solutions. Here we probe the pathway leading to fast association between TEM1 β-lactamase and its inhibitor protein BLIP in crowded s...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2012.08.009

    authors: Phillip Y,Harel M,Khait R,Qin S,Zhou HX,Schreiber G

    更新日期:2012-09-05 00:00:00

  • Structural studies of synthetic filaments prepared from column-purified myosin.

    abstract::Synthetic filaments prepared from column-purified rabbit skeletal myosin by slow dialysis exhibit characteristic bipolar organization and 14-nm axial subunit spacing. Backbone substructure can be discerned in high resolution micrographs in the form of striations of 3--4-nm width and slight angular tilt from the direct...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(79)85226-1

    authors: Koretz JF

    更新日期:1979-09-01 00:00:00

  • Chlorophyll ring deformation modulates Qy electronic energy in chlorophyll-protein complexes and generates spectral forms.

    abstract::The possibility that the chlorophyll (chl) ring distortions observed in the crystal structures of chl-protein complexes are involved in the transition energy modulation, giving rise to the spectral forms, is investigated. The out-of-plane chl-macrocycle distortions are described using an orthonormal set of deformation...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.104554

    authors: Zucchelli G,Brogioli D,Casazza AP,Garlaschi FM,Jennings RC

    更新日期:2007-09-15 00:00:00

  • Components of sodium and chloride flux across toad bladder.

    abstract::The effect of transepithelial potential difference (psi) on Na and Cl flux across toad bladder was assessed by measuring isotopic flux between identical media at various values of psi. The contribution of edge damage to ionic permeability was eliminated, resulting in relatively high spontaneous psi (-97 +/-4 mv) and l...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(72)86089-2

    authors: Walser M

    更新日期:1972-04-01 00:00:00

  • An error analysis for two-state protein-folding kinetic parameters and phi-values: progress toward precision by exploring pH dependencies on Leffler plots.

    abstract::The interpretation of phi-values has led to an understanding of the folding transition state ensemble of a variety of proteins. Although the main guidelines and equations for calculating phi are well established, there remains some controversy about the quality of the numerical values obtained. By analyzing a complete...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.113241

    authors: Cobos ES,Candel AM,Martinez JC

    更新日期:2008-06-01 00:00:00

  • Effect of Phosphorylation on a Human-like Osteopontin Peptide.

    abstract::The last decade established that the dynamic properties of the phosphoproteome are central to function and its modulation. The temporal dimension of phosphorylation effects remains nonetheless poorly understood, particularly for intrinsically disordered proteins. Osteopontin, selected for this study due to its key rol...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2017.03.005

    authors: Lenton S,Grimaldo M,Roosen-Runge F,Schreiber F,Nylander T,Clegg R,Holt C,Härtlein M,García Sakai V,Seydel T,Marujo Teixeira SC

    更新日期:2017-04-25 00:00:00

  • Mg2+-paracrystal formation of tropomyosin as a condensation phenomenon. Effects of pH, salt, temperature, and troponin binding.

    abstract::Tropomyosin (Tm) paracrystal formation induced by Mg2+ was studied by monitoring increases in light scattering. Paracrystals formed above a critical Tm concentration with lag phases in the time courses at pH 7.5 and 6.0, indicating that condensation polymerization processes are involved. The kinetic data at pH 7.5 rea...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(89)82655-4

    authors: Ishii Y,Lehrer SS

    更新日期:1989-07-01 00:00:00

  • Regulation of nerve terminal calcium channel selectivity by a weak acid site.

    abstract::The effects of low pH, and of alkaline earth cations, were examined on calcium uptake by pinched-off nerve terminals (synaptosomes). This uptake appears to be mediated by voltage-sensitive Ca channels (J. Physiol. 247:617, 1975). Ca uptake was measured in low (5 mM) or high (77 mM) potassium media. The extra uptake pr...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(79)85253-4

    authors: Nachshen DA,Blaustein MP

    更新日期:1979-05-01 00:00:00

  • Comparison of the electrophoretic and hydrodynamic properties of DNA and RNA oligonucleotide duplexes.

    abstract::The electrophoretic behavior of defined DNA and RNA oligonucleotide duplexes from 10 to 20 bp in length has been investigated as a function of salt conditions, gel concentration, and temperature. The RNA oligomers migrated much more slowly than the DNA oligomers of the same sequence under all conditions. From sediment...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(97)78185-2

    authors: Bonifacio GF,Brown T,Conn GL,Lane AN

    更新日期:1997-09-01 00:00:00

  • Spiral Wave Propagation in Communities with Spatially Correlated Heterogeneity.

    abstract::Many multicellular communities propagate signals in a directed manner via excitable waves. Cell-to-cell heterogeneity is a ubiquitous feature of multicellular communities, but the effects of heterogeneity on wave propagation are still unclear. Here, we use a minimal FitzHugh-Nagumo-type model to investigate excitable ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2020.02.007

    authors: Zhai X,Larkin JW,Süel GM,Mugler A

    更新日期:2020-04-07 00:00:00

  • Recognition and interactions controlling the assemblies of beta barrel domains.

    abstract::We present a qualitative computer graphics approach to the characterization of forces important to the assembly of beta domains that should have general utility for examining protein interactions and assembly. In our approach, the nature of the molecular surface buried by the domain contacts, the specificity of the re...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(86)83634-7

    authors: Getzoff ED,Tainer JA,Olson AJ

    更新日期:1986-01-01 00:00:00

  • Photoreverse reaction dynamics of octopus rhodopsin.

    abstract::Photoreverse reactions of octopus rhodopsin (Rh) from acid-metarhodopsin (Acid-Meta), which is the final product of the photoreaction of Rh, to Rh were studied by the time-resolved transient absorption and transient grating methods. The time course of the absorption signal showed a rapid change within 500 ns followed ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.106.101741

    authors: Inoue K,Tsuda M,Terazima M

    更新日期:2007-05-15 00:00:00

  • Dynamic light-scattering evidence for the flexibility of native muscle thin filaments.

    abstract::We have obtained clear evidence for the flexibility of native scallop adductor thin filaments by studying the temperature and ionic strength dependence of the average decay constants obtained from intensity fluctuation spectroscopic (IFS) measurements. The low-angle (10-25 degrees ), average decay constants obtained f...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(80)85116-2

    authors: Newman J,Carlson FD

    更新日期:1980-01-01 00:00:00