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Effective interactions in protein-salt solutions approaching liquid-liquid phase separation

We present an experimental study combined with a theoretical discussion of the effective interactions in protein solutions approaching a liquid-liquid phase separation (LLPS) induced by addition of multivalent metal ions. The reduced second virial coefficient, B2/B2HS, is used to describe the interaction and discussed with theoretical predictions for colloidal systems. We have determined the salt

Protein cluster formation in aqueous solution in the presence of multivalent metal ions-a light scattering study

The formation of protein clusters as precursors for crystallization and phase separation is of fundamental and practical interest in protein science. Using multivalent ions, the strengths of both long-range Coulomb repulsion and short-range attraction can be tuned in protein solutions, representing a well-controlled model system to study static and dynamic properties of clustering during the trans

Ion-activated attractive patches as a mechanism for controlled protein interactions

The understanding of protein interactions to control phase and nucleation behavior of protein solutions is an important challenge for soft matter, biological and medical research. Here, we present ion bridges of multivalent cations between proteins as an ion-activated mechanism for patchy interaction that is directly supported by experimental findings in protein crystals. A deep understanding of e

Competing salt effects on phase behavior of protein solutions : Tailoring of protein interaction by the binding of multivalent ions and charge screening

The phase behavior of protein solutions is affected by additives such as crowder molecules or salts. In particular, upon addition of multivalent counterions, a reentrant condensation can occur; i.e., protein solutions are stable for low and high multivalent ion concentrations but aggregating at intermediate salt concentrations. The addition of monovalent ions shifts the phase boundaries to higher

Diffusion and dynamics of γ-globulin in crowded aqueous solutions

Dynamics in protein solutions is essential for both protein function and cellular processes. The hierarchical complexity of global protein diffusion, side-chain diffusion, and microscopic motions of chemical groups renders a complete understanding challenging. We present results from quasi-elastic neutron scattering on protein solutions of γ-globulin over a wide range of volume fractions. Translat

The role of cluster formation and metastable liquid - Liquid phase separation in protein crystallization

We discuss the phase behavior and in particular crystallization of a model globular protein (beta-lactoglobulin) in solution in the presence of multivalent electrolytes. It has been shown previously that negatively charged globular proteins at neutral pH in the presence of multivalent counterions undergo a "re-entrant condensation (RC)" phase behavior (Zhang et al., Phys. Rev. Lett., 2008, 101, 14

Hydration and interactions in protein solutions containing concentrated electrolytes studied by small-angle scattering

During protein crystallization and purification, proteins are commonly found in concentrated salt solutions. The exact interplay of the hydration shell, the salt ions, and protein-protein interactions under these conditions is far from being understood on a fundamental level, despite the obvious practical relevance. We have studied a model globular protein (bovine serum albumin, BSA) in concentrat

Interplay of pH and binding of multivalent metal ions : Charge inversion and reentrant condensation in protein solutions

Tuning of protein surface charge is a fundamental mechanism in biological systems. Protein charge is regulated in a physiological context by pH and interaction with counterions. We report on charge inversion and the related reentrant condensation in solutions of globular proteins with different multivalent metal cations. In particular, we focus on the changes in phase behavior and charge regulatio

Protein self-diffusion in crowded solutions

Macromolecular crowding in biological media is an essential factor for cellular function. The interplay of intermolecular interactions at multiple time and length scales governs a fine-tuned system of reaction and transport processes, including particularly protein diffusion as a limiting or driving factor. Using quasielastic neutron backscattering, we probe the protein self-diffusion in crowded a

Protein diffusion in crowded electrolyte solutions

We report on a combined cold neutron backscattering and spin-echo study of the short-range and long-range nanosecond diffusion of the model globular protein bovine serum albumin (BSA) in aqueous solution as a function of protein concentration and NaCl salt concentration. Complementary small angle X-ray scattering data are used to obtain information on the correlations of the proteins in solution.

Dynamics of highly concentrated protein solutions around the denaturing transition

Using both quasi-elastic and fixed-window neutron spectroscopy, we study the dynamics of highly concentrated aqueous protein solutions of bovine serum albumin around the denaturing transition. For the temperature range 280 K < T < 370 K, the total mean-squared displacement 〈u 2〉 is recorded. Below and above the denaturing, we observe that 〈u 2〉 increases monotonically with T, but at the denaturing

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

We demonstrate that a metastable liquid-liquid phase separation (LLPS) in protein aqueous solutions can be induced by multivalent metal ions at room temperature. We determine the salt and protein partitioning in the two coexisting phases. The structure factor obtained by small angle X-ray scattering provides direct evidence for a short-ranged attraction, which leads to the metastability of the LLP

Viscosity and diffusion : Crowding and salt effects in protein solutions

We report on a joint experimental-theoretical study of collective diffusion in, and static shear viscosity of solutions of bovine serum albumin (BSA) proteins, focusing on the dependence on protein and salt concentration. Data obtained from dynamic light scattering and rheometric measurements are compared to theoretical calculations based on an analytically treatable spheroid model of BSA with iso

Weak Shape Anisotropy Leads to a Nonmonotonic Contribution to Crowding, Impacting Protein Dynamics under Physiologically Relevant Conditions

The effect of a nonspherical particle shape on the dynamics in crowded solutions presents a significant challenge for a comprehensive understanding of interaction and structural relaxation in biological and soft matter. We report that small deviations from a spherical shape induce a nonmonotonic contribution to the crowding effect on the short-time cage diffusion compared with spherical systems, u

Reentrant Phase Behavior in Protein Solutions Induced by Multivalent Salts: Strong Effect of Anions Cl– Versus NO3–

In this work, the effects of the two anions Cl– and NO3– on the phase behavior of bovine serum albumin (BSA) in solution with trivalent salts are compared systematically. In the presence of trivalent metal salts, negatively charged proteins such as BSA in solution undergo a reentrant condensation (RC) phase behavior, which has been established for several proteins with chlorides of trivalent salts

Doing the unknown. Spa activities in a nursing homes

An ethnomethodological point of departure is that people rely on shared knowledge when mutually accomplishing everyday situations. Whereas most residents in a nursing home have a reasonable previous knowledge of events such as bingo or Christmas dinners, other activities such as pub evenings and spa activities are unfamiliar. Using ethnographic data from a Swedish nursing home with a “sport and sp

Assessing the Sustainability of Decentralized Wastewater Treatment Systems in Rwanda

Kigali city, the capital of Rwanda, relies on decentralized, on-site, wastewater systems due to the absence of central sewerage systems and the limited finances to construct sustainable sanitation infrastructures. However, the city has increasingly shown failures in managing these on-site systems either at individual or collective levels. This study aims at assessing the sustainability of the oper

Retrospective assessment of menstrual cycle length in patients with breast cancer, in patients with benign breast disease, and in women without breast disease

The length of the menstrual cycle was compared in women with breast cancer, women with benign breast disease, and controls. Older women in general tended to report shorter menstrual cycles (P < 0.05). After correction for the age difference, breast cancer patients still reported a shorter average menstrual cycle length than benign breast disease patients and controls (P < 0.006). Very short cycles

Hypophyseal tumor and gynecomastia preceding bilateral breast cancer development in a man

The case is reported of a 48‐year‐old man who, 26 years after treatment for a hypophyseal tumor and 11 years after the onset of bilateral gynecomastia, developed cancer of the left breast. Ten years after the first breast cancer operation a new cancer developed in his right breast. Hormonal investigation at the time of the second breast cancer operation revealed a low S‐FSH and a relative estrogen