scholarly journals Repulsive electrostatic interactions modulate dense and dilute phase properties of biomolecular condensates

2020 ◽  
Author(s):  
Michael D. Crabtree ◽  
Jack Holland ◽  
Purnima Kompella ◽  
Leon Babl ◽  
Noah Turner ◽  
...  
Keyword(s):  
Germ Cell ◽  
Electrostatic Interactions ◽  
Negative Charge ◽  
Weak Interactions ◽  
Fine Tuning ◽  
Eukaryotic Cells ◽  
Biochemical Reactions ◽  
Net Charge ◽  
Solvent Properties

AbstractLiquid-like membraneless organelles form via multiple, weak interactions between biomolecules. The resulting condensed states constitute novel solvent environments inside eukaryotic cells that partition biomolecules and may favour particular biochemical reactions. Here we demonstrate that, in addition to attractive interactions, repulsive electrostatic interactions modulate condensate properties. We find that net charge modulates the formation, morphology and solvent properties of model Ddx4 condensates in cells and in vitro and that a net negative charge is conserved across germ cell-specific Ddx4 orthologues. This conserved net charge provides a sensitivity to multivalent cations that is not observed in somatic paralogues. The disfavouring effect of a net negative charge in Ddx4 orthologues appears to be offset by increased charge patterning, indicating that fine tuning of both attractive and repulsive interactions can create responsive solvent environments inside biomolecular condensates.

The Hierarchic Order of Intermediate Filament Structure and Assembly

1985 ◽  
Vol 43 ◽  
pp. 722-725
Author(s):  
U. Aebi ◽  
E.C. Glavaris ◽  
R. Eichner
Keyword(s):  
Tissue Specificity ◽  
Structural Model ◽  
Eukaryotic Cells ◽  
Cdna Sequencing ◽  
Filament Structure ◽  
Keratin Filaments ◽  
Isoelectric Points ◽  
Immunological Crossreactivity

Five different classes of intermediate-sized filaments (IFs) have been identified in differentiated eukaryotic cells: vimentin in mesenchymal cells, desmin in muscle cells, neurofilaments in nerve cells, glial filaments in glial cells and keratin filaments in epithelial cells. Despite their tissue specificity, all IFs share several common attributes, including immunological crossreactivity, similar morphology (e.g. about 10 nm diameter - hence ‘10-nm filaments’) and the ability to reassemble in vitro from denatured subunits into filaments virtually indistinguishable from those observed in vivo. Further more, despite their proteinchemical heterogeneity (their MWs range from 40 kDa to 200 kDa and their isoelectric points from about 5 to 8), protein and cDNA sequencing of several IF polypeptides (for refs, see 1,2) have provided the framework for a common structural model of all IF subunits.

Wheat Germ Cell-Free Translation System as a Tool for In vitro Selection of Functional Proteins

2002 ◽  
Vol 5 (6) ◽  
pp. 473-480
Author(s):  
Bentham Science Publisher A.N. Alexandrov ◽  
Bentham Science Publisher V.Yu. Alakhov ◽  
Bentham Science Publisher A.I. Miroshnikov
Keyword(s):  
Germ Cell ◽  
Wheat Germ ◽  
In Vitro Selection ◽  
Translation System ◽  
Free Translation ◽  
Selection Of

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

scholarly journals Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikas A. Tillu ◽  
James Rae ◽  
Ya Gao ◽  
Nicholas Ariotti ◽  
Matthias Floetenmeyer ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Membrane Lipid ◽  
Membrane Curvature ◽  
Caveolin 1 ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Solution Generation ◽  
Endosomal System ◽  
Disordered Regions

AbstractCaveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

scholarly journals Tuning the network charge of biohybrid hydrogel matrices to modulate the release of SDF-1

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sebastian Kühn ◽  
Joanna Freyse ◽  
Passant Atallah ◽  
Jörg Rademann ◽  
Uwe Freudenberg ◽  
...  
Keyword(s):  
Bone Repair ◽  
Negative Charge ◽  
Polymer Networks ◽  
Signaling Molecules ◽  
Treatment Modalities ◽  
Precise Control ◽  
Integral Density ◽  
New Treatment ◽  
Two Parameters

Abstract The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.

scholarly journals Oxygen tension modulates the mitochondrial genetic bottleneck and influences the segregation of a heteroplasmic mtDNA variant in vitro

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikael G. Pezet ◽  
Aurora Gomez-Duran ◽  
Florian Klimm ◽  
Juvid Aryaman ◽  
Stephen Burr ◽  
...  
Keyword(s):  
Germ Cell ◽  
Oxygen Tension ◽  
Germ Line ◽  
Embryonic Stem ◽  
Mitochondrial Diseases ◽  
Genetic Bottleneck ◽  
Cellular Mechanisms ◽  
Germ Cell Specification ◽  
Vitro Model

AbstractMost humans carry a mixed population of mitochondrial DNA (mtDNA heteroplasmy) affecting ~1–2% of molecules, but rapid percentage shifts occur over one generation leading to severe mitochondrial diseases. A decrease in the amount of mtDNA within the developing female germ line appears to play a role, but other sub-cellular mechanisms have been implicated. Establishing an in vitro model of early mammalian germ cell development from embryonic stem cells, here we show that the reduction of mtDNA content is modulated by oxygen and reaches a nadir immediately before germ cell specification. The observed genetic bottleneck was accompanied by a decrease in mtDNA replicating foci and the segregation of heteroplasmy, which were both abolished at higher oxygen levels. Thus, differences in oxygen tension occurring during early development likely modulate the amount of mtDNA, facilitating mtDNA segregation and contributing to tissue-specific mutation loads.

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