Charge-controlled metastable liquid–liquid phase separation in protein solutions as a universal pathway towards crystallization

Zhang, Fajun; Roth, Roland; Wolf, Melanie; Roosen-Runge, Felix; Skoda, Maximilian W. A.; Jacobs, Robert M.; Stzucki, Michael; Schreiber, Frank

doi:10.1039/c2sm07008a

Cited by 91 publications

(117 citation statements)

References 40 publications

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“…Interestingly, patches are activated by the presence of the ions, allowing external control on the aggregation process. The experimental investigation of Human Serum Albumine in the presence of YCl 3 [57,81] has shown the presence of a metastable liquid-liquid phase transition, in which the coexisting liquid density progressively increases with the number of patches in the system, i.e. the salt concentration.…”

Section: Biological Applicationsmentioning

confidence: 99%

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Equilibrium gels of limited valence colloids

Sciortino

Zaccarelli

2017

Current Opinion in Colloid & Interface Science

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Gels are low-packing arrested states of matter which are able to support stress. On cooling, limited valence colloidal particles form open networks stabilized by the progressive increase of the interparticle bond lifetime. These gels, named equilibrium gels, are the focus of this review article. Differently from other types of colloidal gels, equilibrium gels do not require an underlying phase separation to form. Oppositely, they form in a region of densities deprived of thermodynamic instabilities. Limited valence equilibrium gels neither coarsen nor age with time.

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Section: Biological Applicationsmentioning

confidence: 99%

“…In order, a patchy particle model [53], the DNA-nanostars, the laponite discotic platelet [54], oblate and prolate attractive ellipsoids [55], the Fmoc-FF molecule [56] and a protein in the presence of multivalent salt providing limited interactions [57].…”

Section: Figmentioning

confidence: 99%

Equilibrium gels of limited valence colloids

Sciortino

Zaccarelli

2017

Current Opinion in Colloid & Interface Science

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“…39 Protein-protein interactions in the presence of trivalent salts have been characterized previously for these systems. 40,41 A reentrant condensation phase behavior has been established with a LLPS occurring within the condensed regime in a closed area. The phase behavior was rationalized in terms of an ion-activated patchy interaction.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of liquid–liquid phase separation in protein solutions exhibiting LCST phase behavior studied by time-resolved USAXS and VSANS

et al. 2016

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aWe study the kinetics of the liquid-liquid phase separation (LLPS) and its arrest in protein solutions exhibiting a lower critical solution temperature (LCST) phase behavior using the combination of ultrasmall angle X-ray scattering (USAXS) and very-small angle neutron scattering (VSANS). We employ a previously established model system consisting of bovine serum albumin (BSA) solutions with YCl 3 . We follow the phase transition from sub-second to 10 4 s upon an off-critical temperature jump. After a temperature jump, the USAXS profiles exhibit a peak that grows in intensity and shifts to lower q values

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“…This anomalous trend, caused by charge reversal, has been shown to be able to induce clustering, liquid-liquid phase separation or crystallization. 12,18,[21][22][23][24][25] The ability to control the phase behavior of protein dispersions show promising opportunities, for example for the production of high quality protein crystals, required for protein structure determination.…”

Section: Introductionmentioning

confidence: 99%

Anomalous Protein–Protein Interactions in Multivalent Salt Solution

et al. 2017

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1 AbstractThe stability of aqueous protein solutions is strongly affected by multivalent ions, which induce ion-ion correlations beyond the scope of classical mean-field theory. Using all-atom Molecular Dynamics (MD) and coarse grained Monte Carlo (MC) simulations, we investigate the interaction between a pair of protein molecules in 3:1 electrolyte solution. In agreement with available experimental findings of "reentrant protein condensation", we observe an anomalous trend in the protein-protein potential of mean force with increasing electrolyte concentration in the order: (i) double-layer repulsion,(ii) ion-ion correlation attraction, (iii) over-charge repulsion, and in excess of 1:1 salt, (iv) non Coulombic attraction. To efficiently sample configurational space we explore hybrid continuum solvent models, applicable to many-protein systems, where weakly coupled ions are treated implicitly, while strongly coupled ones are treated explicitly.Good agreement is found with the primitive model of electrolytes, as well as with atomic models of protein and solvent.2

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Charge-controlled metastable liquid–liquid phase separation in protein solutions as a universal pathway towards crystallization

Cited by 91 publications

References 40 publications

Equilibrium gels of limited valence colloids

Equilibrium gels of limited valence colloids

Kinetics of liquid–liquid phase separation in protein solutions exhibiting LCST phase behavior studied by time-resolved USAXS and VSANS

Anomalous Protein–Protein Interactions in Multivalent Salt Solution

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