Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation.

ABSTRACT: Antibody therapies are typically based on high-concentration formulations that need to be administered subcutaneously. These conditions induce several challenges, inter alia a viscosity suitable for injection, sufficient solution stability, and preservation of molecular function. To obtain systematic insights into the molecular factors, we study the dynamics on the molecular level under strongly varying solution conditions. In particular, we use solutions of antibodies with poly(ethylene glycol), in which simple cooling from room temperature to freezing temperatures induces a transition from a well-dispersed solution into a phase-separated and macroscopically arrested system. Using quasi-elastic neutron scattering during in situ cooling ramps and in prethermalized measurements, we observe a strong decrease in antibody diffusion, while internal flexibility persists to a significant degree, thus ensuring the movement necessary for the preservation of molecular function. These results are relevant for a more dynamic understanding of antibodies in high-concentration formulations, which affects the formation of transient clusters governing the solution viscosity.

SUBMITTER: Girelli A

PROVIDER: S-EPMC8564753 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

In situ observation of macroscopic phase separation in cobalt hexacyanoferrate film.

Project description:Lithium-ion secondary batteries (LIBs) store electric energy via Li+ deintercalation from cathode materials. The Li+ deintercalation frequently drives a first-order phase transition of the cathode material as a result of the Li-ordering or Li-concentration effect and causes a phase separation (PS) into the Li-rich and Li-poor phases. Here, we performed an in situ microscopic investigation of the PS dynamics in thin films of cobalt hexacyanoferrate, LixCo[Fe(CN)6]0.9, against Li+ deintercalation. The thick film (d = 1.5 μm) shows a characteristic macroscopic PS of several tens of μm into the green (Li1.6Co[Fe(CN)6]0.9) and black (Li.6Co[Fe(CN)6]0.9) phases in the x range of 1.0 < x < 1.6. Reflecting the substrate strain, the thin film (d = 0.5 μm) shows no trace of the PS in the entire x region. Our observation suggests that the macroscopic PS plays a significant role in the charge/discharge dynamics of the cathode.

| S-EPMC5311949 | biostudies-literature

Macroscopic phase separation of superconductivity and ferromagnetism in Sr0.5Ce0.5FBiS2-x Se x revealed by ?SR.

Project description:The compound Sr0.5Ce0.5FBiS2 belongs to the intensively studied family of layered BiS2 superconductors. It attracts special attention because superconductivity at T sc ?=?2.8 K was found to coexist with local-moment ferromagnetic order with a Curie temperature T C ?=?7.5 K. Recently it was reported that upon replacing S by Se T C drops and ferromagnetism becomes of an itinerant nature. At the same time T sc increases and it was argued superconductivity coexists with itinerant ferromagnetism. Here we report a muon spin rotation and relaxation study (?SR) conducted to investigate the coexistence of superconductivity and ferromagnetic order in Sr0.5Ce0.5FBiS2-x Se x with x?=?0.5 and 1.0. By inspecting the muon asymmetry function we find that both phases do not coexist on the microscopic scale, but occupy different sample volumes. For x?=?0.5 and x?=?1.0 we find a ferromagnetic volume fraction of ~8 % and ~30 % at T?=?0.25 K, well below T C ?=?3.4 K and T C ?=?3.3 K, respectively. For x?=?1.0 (T sc ?=?2.9 K) the superconducting phase occupies most (~64 %) of the remaining sample volume, as shown by transverse field experiments that probe the Gaussian damping due to the vortex lattice. We conclude ferromagnetism and superconductivity are macroscopically phase separated.

| S-EPMC5727222 | biostudies-other

Capturing Membrane Phase Separation by Dual Resolution Molecular Dynamics Simulations.

Project description:Understanding the lateral organization in plasma membranes remains an open problem and is of great interest to many researchers. Model membranes consisting of coexisting domains are commonly used as simplified models of plasma membranes. The coarse-grained (CG) Martini force field has successfully captured spontaneous separation of ternary membranes into a liquid-disordered and a liquid-ordered domain. With all-atom (AA) models, however, phase separation is much harder to achieve due to the slow underlying dynamics. To remedy this problem, here, we apply the virtual site (VS) hybrid method on a ternary membrane composed of saturated lipids, unsaturated lipids, and cholesterol to investigate the phase separation. The VS scheme couples the two membrane leaflets at CG and AA resolution. We found that the rapid phase separation reached by the CG leaflet can accelerate and guide this process in the AA leaflet.

| S-EPMC8444333 | biostudies-literature

Dehydration entropy drives liquid-liquid phase separation by molecular crowding.

Project description:Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)-a widely used molecular crowder-in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.

| S-EPMC9814391 | biostudies-literature

Macroscopic liquid-state molecular hydrodynamics.

Project description:Experimental evidence and theoretical modeling suggest that piles of confined, high-restitution grains, subject to low-amplitude vibration, can serve as experimentally-accessible analogs for studying a range of liquid-state molecular hydrodynamic processes. Experiments expose single-grain and multiple-grain, collective dynamic features that mimic those either observed or predicted in molecular-scale, liquid state systems, including: (i) near-collision-time-scale hydrodynamic organization of single-molecule dynamics, (ii) nonequilibrium, long-time-scale excitation of collective/hydrodynamic modes, and (iii) long-time-scale emergence of continuum, viscous flow. In order to connect directly observable macroscale granular dynamics to inaccessible and/or indirectly measured molecular hydrodynamic processes, we recast traditional microscale equilibrium and nonequilibrium statistical mechanics for dense, interacting microscale systems into self-consistent, macroscale form. The proposed macroscopic models, which appear to be new with respect to granular physics, and which differ significantly from traditional kinetic-theory-based, macroscale statistical mechanics models, are used to rigorously derive the continuum equations governing viscous, liquid-like granular flow. The models allow physically-consistent interpretation and prediction of observed equilibrium and non-equilibrium, single-grain, and collective, multiple-grain dynamics.

| S-EPMC5282555 | biostudies-literature

Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin.

Project description:We report the observation of liquid-liquid phase separation in a solution of human monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitude of the effective interprotein interactions. Our analysis suggests that additives (HSA in this report), which have moderate attraction with antibody molecules, may be used to forestall undesirable protein condensation in antibody solutions. Our findings are relevant to understanding the stability of pharmaceutical solutions of antibodies and the mechanisms of cryoglobulinemia.

| S-EPMC3189021 | biostudies-literature

Unraveling the molecular interactions involved in phase separation of glucocorticoid receptor.

Project description:BACKGROUND:Functional compartmentalization has emerged as an important factor modulating the kinetics and specificity of biochemical reactions in the nucleus, including those involved in transcriptional regulation. The glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci. While a liquid-liquid phase separation process has been recently proposed to drive the formation of many nuclear compartments, the mechanisms governing the heterogeneous organization of GR in the nucleus and the functional relevance of foci formation remain elusive. RESULTS:We dissected some of the molecular interactions involved in the formation of GR condensates and analyzed the GR structural determinants relevant to this process. We show that GR foci present properties consistent with those expected for biomolecular condensates formed by a liquid-liquid phase separation process in living human cells. Their formation requires an initial interaction of GR with certain chromatin regions at specific locations within the nucleus. Surprisingly, the intrinsically disordered region of GR is not essential for condensate formation, in contrast to many nuclear proteins that require disordered regions to phase separate, while the ligand-binding domain seems essential for that process. We finally show that GR condensates include Mediator, a protein complex involved in transcription regulation. CONCLUSIONS:We show that GR foci have properties of liquid condensates and propose that active GR molecules interact with chromatin and recruit multivalent cofactors whose interactions with additional molecules lead to the formation of a focus. The biological relevance of the interactions occurring in GR condensates supports their involvement in transcription regulation.

| S-EPMC7268505 | biostudies-literature

Cerebral Corpora amylacea are dense membranous labyrinths containing structurally preserved cell organelles.

Project description:Corpora amylacea are cell-derived structures that appear physiologically in the aged human brain. While their histological identification is straightforward, their ultrastructural composition and microenvironment at the nanoscale have remained unclear so far, as has their relevance to aging and certain disease states that involve the sequestration of toxic cellular metabolites. Here, we apply correlative serial block-face scanning electron microscopy and transmission electron tomography to gain three-dimensional insight into the ultrastructure and surrounding microenvironment of cerebral Corpora amylacea in the human brainstem and hippocampal region. We find that cerebral Corpora amylacea are composed of dense labyrinth-like sheets of lipid membranes, contain vesicles as well as morphologically preserved mitochondria, and are in close proximity to blood vessels and the glymphatic system, primarily within the cytoplasm of perivascular glial cells. Our results clarify the nature of cerebral Corpora amylacea and provide first hints on how they may arise and develop in the aging brain.

| S-EPMC6303404 | biostudies-literature

Enhanced Phase Separation Mediated Oncogenicity

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-24 | GSE211456 | GEO

Molecular Mass Affects the Phase Separation of Aqueous PEG-Polycation Block Copolymer.

Project description:Mechanisms of the phase separation and remixing of cationic PEG-containing block copolymers have been investigated in aqueous lithium triflate solutions. The polycation was poly(vinylbenzyl trimethylammonium triflate). We have previously reported on one such block copolymer, which upon cooling of a hot clear solution first underwent phase separation into a turbid colloid and, later, partially cleared again with further cooling. To better understand the balance of various interactions in the solutions/dispersions, a series of polymers with varying DP of the cationic block was synthesized. From one of the polymers, the alkyl end group (a fragment of the chain transfer agent) was removed. The length of the cationic block affected critically the behavior, but the hydrophobic end group had a minimal effect. Polymers with a short cationic block turn cloudy and partially clear again during a temperature decrease, whereas those with a long cationic block phase separate and slowly precipitate and remix only when heated. Phase separation takes place via particle formation, and we suggest different mechanisms for colloidal stabilization of particles composed of short or long chains.

| S-EPMC6748676 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data