scholarly journals Gelation Impairs Phase Separation and Small Molecule Migration in Polymer Mixtures

Polymers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1576
Author(s):  
Biswaroop Mukherjee ◽  
Buddhapriya Chakrabarti
Keyword(s):  
Phase Separation ◽  
Rational Design ◽  
Surface Segregation ◽  
Multiscale Methods ◽  
Coarse Grained ◽  
Polymer Gel ◽  
Polymer Mixtures ◽  
Separation Processes ◽  
Surface Migration ◽  
Wide Range

Surface segregation of the low molecular weight component of a polymeric mixture is a ubiquitous phenomenon that leads to degradation of industrial formulations. We report a simultaneous phase separation and surface migration phenomena in oligomer–polymer ( O P ) and oligomer–gel ( O G ) systems following a temperature quench that induces demixing of components. We compute equilibrium and time varying migrant (oligomer) density profiles and wetting layer thickness in these systems using coarse grained molecular dynamics (CGMD) and mesoscale hydrodynamics (MH) simulations. Such multiscale methods quantitatively describe the phenomena over a wide range of length and time scales. We show that surface migration in gel–oligomer systems is significantly reduced on account of network elasticity. Furthermore, the phase separation processes are significantly slowed in gels leading to the modification of the well known Lifshitz–Slyozov–Wagner (LSW) law ℓ ( τ ) ∼ τ 1 / 3 . Our work allows for rational design of polymer/gel–oligomer mixtures with predictable surface segregation characteristics that can be compared against experiments.

scholarly journals Charge-Driven Condensation of RNA and Proteins Suggests Broad Role of Phase Separation in Cytoplasmic Environments

2020 ◽  
Author(s):  
Bercem Dutagaci ◽  
Grzegorz Nawrocki ◽  
Joyce Goodluck ◽  
Ali Akbar Ashkarran ◽  
Charles G. Hoogstraten ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Molecular Size ◽  
Liquid Phase Separation ◽  
Coarse Grained ◽  
Biological Macromolecules ◽  
Separation Processes ◽  
Cellular Environment ◽  
Liquid Liquid Phase Separation

ABSTRACTPhase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well established drivers of liquid-liquid phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Condensates retain liquid character and phase diagrams are mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.STATEMENT OF SIGNIFICANCELiquid-liquid phase separation has been recognized as a key mechanism for forming membrane-less organelles in cells. Commonly discussed mechanisms invoke a role of disordered peptides and specific multi-valent interactions. We report here phase separation of RNA and proteins based on a more universal principle of charge complementarity that does not require disorder or specific interactions. The findings are supported by coarse-grained simulations, theory, and experimental validation via microscopy and spectroscopy. The broad implication of this work is that condensate formation may be a universal phenomenon in biological systems.

scholarly journals Martini Coarse-Grained Models of Imidazolium-Based Ionic Liquids: From Nanostructural Organization to Liquid-Liquid Extraction

2020 ◽  
Author(s):  
Luis Itza Vazquez-Salazar ◽  
Michele Selle ◽  
Alex H. de Vries ◽  
Siewert-Jan Marrink ◽  
Paulo C. T. Souza
Keyword(s):  
Ionic Liquids ◽  
Force Field ◽  
Rational Design ◽  
Value Added ◽  
Liquid Extraction ◽  
Coarse Grained ◽  
Great Success ◽  
Liquid Liquid Extraction ◽  
Martini Force Field ◽  
Wide Range

<div> <div> <div> <p>Ionic liquids (IL) are remarkable green solvents, which find applications in many areas of nano- and biotechnology including extraction and purification of value-added compounds or fine chemicals. These liquid salts possess versatile solvation properties that can be tuned by modifications in the cation or anion structure. So far, in contrast to the great success of theoretical and computational methodologies applied to other fields, only a few IL models have been able to bring insights towards the rational design of such solvents. In this work, we develop coarse-grained (CG) models for imidazolium-based ILs using a new version of the Martini force field. The model is able to reproduce the main structural properties of pure ILs, including spatial heterogeneity and global densities over a wide range of temperatures. More importantly, given the high intermolecular compatibility of the Martini force field, this new IL CG model opens the possibility of large-scale simulations of liquid-liquid extraction experiments. As examples, we show two applications, namely the extraction of aromatic molecules from a petroleum oil model and the extraction of omega-3 polyunsaturated fatty acids from a fish oil model. In semi-quantitative agreement with the experiments, we show how the extraction capacity and selectivity of the IL could be affected by the cation chain length or addition of co-solvents. </p> </div> </div> </div>

scholarly journals Inserting small molecules across membrane mixtures: Insight from the potential of mean force

2019 ◽  
Author(s):  
Alessia Centi ◽  
Arghya Dutta ◽  
Sapun H. Parekh ◽  
Tristan Bereau
Keyword(s):  
Phase Separation ◽  
Small Molecules ◽  
Lipid Membrane ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Conformational Space ◽  
Coarse Grained ◽  
Computationally Efficient ◽  
Computational Screening ◽  
Wide Range

ABSTRACTSmall solutes have been shown to alter the lateral organization of cell membranes and reconstituted phospholipid bilayers; however, the mechanisms by which these changes happen are still largely unknown. Traditionally, both experiment and simulation studies have been restricted to testing only a few compounds at a time, failing to identify general molecular descriptors or chemical properties that would allow extrapolating beyond the subset of considered solutes. In this work, we probe the competing energetics of inserting a solute in different membrane environments by means of the potential of mean force. We show that these calculations can be used as a computationally-efficient proxy to establish whether a solute will stabilize or destabilize domain phase separation. Combined with umbrella sampling simulations and coarse-grained molecular dynamics simulations, we are able to screen solutes across a wide range of chemistries and polarities. Our results indicate that, for the system under consideration, preferential partitioning and therefore effectiveness in altering membrane phase separation are strictly linked to the location of insertion in the bilayer (i.e., midplane or interface). Our approach represents a fast and simple tool for obtaining structural and thermodynamic insight into the partitioning of small molecules between lipid domains and its relation to phase separation, ultimately providing a platform for identifying the key determinants of this process.SIGNIFICANCEIn this work we explore the relationship between solute chemistry and the thermodynamics of insertion in a mixed lipid membrane. By combining a coarse-grained resolution and umbrella-sampling simulations we efficiently sample conformational space to study the thermodynamics of phase separation. We demonstrate that measures of the potential of mean force—a computationally-efficient quantity—between different lipid environments can serve as a proxy to predict a compound’s ability to alter the thermodynamics of the lipid membrane. This efficiency allows us to set up a computational screening across many compound chemistries, thereby gaining insight beyond the study of a single or a handful of compounds.

scholarly journals Liquid-liquid microphase separation leads to formation of membraneless organelles

2019 ◽  
Author(s):  
Srivastav Ranganathan ◽  
Eugene Shakhnovich
Keyword(s):  
Phase Separation ◽  
Rational Design ◽  
Microphase Separation ◽  
Morphological Changes ◽  
Specific Interaction ◽  
Coarse Grained ◽  
High Concentrations ◽  
Macrophase Separation

AbstractProteins and nucleic acids can spontaneously self-assemble into membraneless droplet-like compartments, both in vitro and in vivo. A key component of these droplets are multi-valent proteins that possess several adhesive domains with specific interaction partners (whose number determines total valency of the protein) separated by disordered regions. Here, using multi-scale simulations we show that such proteins self-organize into micro-phase separated droplets of various sizes as opposed to the Flory-like macro-phase separated equilibrium state of homopolymers or equilibrium physical gels. We show that the micro-phase separated state is a dynamic outcome of the interplay between two competing processes: a diffusion-limited encounter between proteins, and the dynamics within small clusters that results in exhaustion of available valencies whereby all specifically interacting domains find their interacting partners within smaller clusters, leading to arrested phase separation. We first model these multi-valent chains as bead-spring polymers with multiple adhesive domains separated by semi-flexible linkers and use Langevin Dynamics (LD) to assess how key timescales depend on the molecular properties of associating polymers. Using the time-scales from LD simulations, we develop a coarse-grained kinetic model to study this phenomenon at longer times. Consistent with LD simulations, the macro-phase separated state was only observed at high concentrations and large interaction valencies. Further, in the regime where cluster sizes approach macro-phase separation, the condensed phase becomes dynamically solid-like, suggesting that it might no longer be biologically functional. Therefore, the micro-phase separated state could be a hallmark of functional droplets formed by proteins with the sticker-spacer architecture.Significance statementMembraneless organells (MO) are ubiquitous in ‘healthy’ living cells, with an altered state in disease. Their formation is likened to liquid-liquid phase separation (LLPS) between MO-forming proteins. However most models of LLPS predict complete macrophase separation while in reality MO’s are small droplets of various sizes, which are malleable to rapid morphological changes. Here we present a microscopic multiscale theoretical study of thermodynamics and kinetics of formation of MO. We show that MO’s are long-living dynamic structures formed as a result of arrested macrophase separation. Our study provides a direct link beween the molecular properies of MO-forming proteins and the morphology and dynamics of MO paving a path to rational design and control of MO.

scholarly journals Modeling and simulation of protein–surface interactions: achievements and challenges

2016 ◽  
Vol 49 ◽  
Author(s):  
Musa Ozboyaci ◽  
Daria B. Kokh ◽  
Stefano Corni ◽  
Rebecca C. Wade
Keyword(s):  
Modeling And Simulation ◽  
Rational Design ◽  
Surface Interactions ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Surface Binding ◽  
Protein Surface ◽  
Material Surfaces ◽  
Wide Range ◽  
Protein Surface Interactions

AbstractUnderstanding protein–inorganic surface interactions is central to the rational design of new tools in biomaterial sciences, nanobiotechnology and nanomedicine. Although a significant amount of experimental research on protein adsorption onto solid substrates has been reported, many aspects of the recognition and interaction mechanisms of biomolecules and inorganic surfaces are still unclear. Theoretical modeling and simulations provide complementary approaches for experimental studies, and they have been applied for exploring protein–surface binding mechanisms, the determinants of binding specificity towards different surfaces, as well as the thermodynamics and kinetics of adsorption. Although the general computational approaches employed to study the dynamics of proteins and materials are similar, the models and force-fields (FFs) used for describing the physical properties and interactions of material surfaces and biological molecules differ. In particular, FF and water models designed for use in biomolecular simulations are often not directly transferable to surface simulations and vice versa. The adsorption events span a wide range of time- and length-scales that vary from nanoseconds to days, and from nanometers to micrometers, respectively, rendering the use of multi-scale approaches unavoidable. Further, changes in the atomic structure of material surfaces that can lead to surface reconstruction, and in the structure of proteins that can result in complete denaturation of the adsorbed molecules, can create many intermediate structural and energetic states that complicate sampling. In this review, we address the challenges posed to theoretical and computational methods in achieving accurate descriptions of the physical, chemical and mechanical properties of protein-surface systems. In this context, we discuss the applicability of different modeling and simulation techniques ranging from quantum mechanics through all-atom molecular mechanics to coarse-grained approaches. We examine uses of different sampling methods, as well as free energy calculations. Furthermore, we review computational studies of protein–surface interactions and discuss the successes and limitations of current approaches.

scholarly journals Structure of biomolecular condensates from dissipative particle dynamics simulations

2019 ◽  
Author(s):  
Julian C. Shillcock ◽  
Maelick Brochut ◽  
Etienne Chénais ◽  
John H. Ipsen
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Intrinsically Disordered Proteins ◽  
Liquid Phase Separation ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Wide Range ◽  
End Caps ◽  
Liquid Liquid Phase Separation

ABSTRACTPhase separation of immiscible fluids is a common phenomenon in polymer chemistry, and is recognized as an important mechanism by which cells compartmentalize their biochemical reactions. Biomolecular condensates are condensed fluid droplets in cells that form by liquid-liquid phase separation of intrinsically-disordered proteins. They have a wide range of functions and are associated with chronic neurodegenerative diseases in which they become pathologically rigid. Intrinsically-disordered proteins are conformationally flexible and possess multiple, distributed binding sites for each other or for RNA. However, it remains unclear how their material properties depend on the molecular structure of the proteins. Here we use coarse-grained simulations to explore the phase behavior and structure of a model biomolecular condensate composed of semi-flexible polymers with attractive end-caps in a good solvent. Although highly simplified, the model contains the minimal molecular features that are sufficient to observe liquid-liquid phase separation of soluble polymers. The polymers condense into a porous, three-dimensional network in which their end-caps reversibly bind at junctions. The spatial separation of connected junctions scales with the polymer backbone length as a self-avoiding random walk over a wide range of concentration with a weak affinity-dependent prefactor. By contrast, the average number of polymers that meet at the junctions depends strongly on the end-cap affinity but only weakly on the polymer length. The regularity and porosity of the condensed network suggests a mechanism for cells to regulate biomolecular condensates. Interaction sites along a protein may be turned on or off to modulate the condensate’s porosity and tune the diffusion and interaction of additional proteins.

scholarly journals Phase separation and surface segregation in ceria–zirconia solid solutions

2011 ◽  
Vol 467 (2131) ◽  
pp. 1925-1938 ◽  
Author(s):  
Ricardo Grau-Crespo ◽  
Nora H. de Leeuw ◽  
Said Hamad ◽  
Umesh V. Waghmare
Keyword(s):  
Phase Separation ◽  
High Temperatures ◽  
Solid Solutions ◽  
Density Functional ◽  
Surface Segregation ◽  
Equilibrium Concentration ◽  
Density Functional Theory Calculations ◽  
Atomic Scale ◽  
Functional Theory ◽  
Wide Range

Using a combination of density functional theory calculations and statistical mechanics, we show that a wide range of intermediate compositions of ceria–zirconia solid solutions are thermodynamically metastable with respect to phase separation into Ce-rich and Zr-rich oxides. We estimate that the maximum equilibrium concentration of Zr in CeO 2 at 1373 K is approximately 2 per cent, and therefore, equilibrated samples with higher Zr content are expected to exhibit heterogeneity at the atomic scale. We also demonstrate that in the vicinity of the (111) surface, cation redistribution at high temperatures will occur with significant Ce enrichment of the surface, which we attribute to the more covalent character of Zr–O bonds compared with Ce–O bonds. Although the kinetic barriers for cation diffusion normally prevent the decomposition/segregation of ceria–zirconia solid solutions in typical catalytic applications, the separation behaviour described here can be expected to occur in modern three-way catalytic converters, where very high temperatures are reached.

scholarly journals Martini Coarse-Grained Models of Imidazolium-Based Ionic Liquids: From Nanostructural Organization to Liquid-Liquid Extraction

2020 ◽  
Author(s):  
Luis Itza Vazquez-Salazar ◽  
Michele Selle ◽  
Alex H. de Vries ◽  
Siewert-Jan Marrink ◽  
Paulo C. T. Souza
Keyword(s):  
Ionic Liquids ◽  
Force Field ◽  
Rational Design ◽  
Value Added ◽  
Liquid Extraction ◽  
Coarse Grained ◽  
Great Success ◽  
Liquid Liquid Extraction ◽  
Martini Force Field ◽  
Wide Range

<div> <div> <div> <p>Ionic liquids (IL) are remarkable green solvents, which find applications in many areas of nano- and biotechnology including extraction and purification of value-added compounds or fine chemicals. These liquid salts possess versatile solvation properties that can be tuned by modifications in the cation or anion structure. So far, in contrast to the great success of theoretical and computational methodologies applied to other fields, only a few IL models have been able to bring insights towards the rational design of such solvents. In this work, we develop coarse-grained (CG) models for imidazolium-based ILs using a new version of the Martini force field. The model is able to reproduce the main structural properties of pure ILs, including spatial heterogeneity and global densities over a wide range of temperatures. More importantly, given the high intermolecular compatibility of the Martini force field, this new IL CG model opens the possibility of large-scale simulations of liquid-liquid extraction experiments. As examples, we show two applications, namely the extraction of aromatic molecules from a petroleum oil model and the extraction of omega-3 polyunsaturated fatty acids from a fish oil model. In semi-quantitative agreement with the experiments, we show how the extraction capacity and selectivity of the IL could be affected by the cation chain length or addition of co-solvents. </p> </div> </div> </div>

Patterns in diversity and composition of the microbenthos of subarctic intertidal beaches with different morphodynamics

2020 ◽  
Vol 648 ◽  
pp. 19-38
Author(s):  
AI Azovsky ◽  
YA Mazei ◽  
MA Saburova ◽  
PV Sapozhnikov
Keyword(s):  
Species Abundance ◽  
Abundance Ratio ◽  
Wave Action ◽  
Coarse Grained ◽  
Sediment Properties ◽  
Β Diversity ◽  
Α Diversity ◽  
Wide Range ◽  
Similar Mode ◽  
Abundance And Diversity

Diversity and composition of benthic diatom algae and ciliates were studied at several beaches along the White and Barents seas: from highly exposed, reflective beaches with coarse-grained sands to sheltered, dissipative silty-sandy flats. For diatoms, the epipelic to epipsammic species abundance ratio was significantly correlated with the beach index and mean particle size, while neither α-diversity measures nor mean cell length were related to beach properties. In contrast, most of the characteristics of ciliate assemblages (diversity, total abundance and biomass, mean individual weight and percentage of karyorelictids) demonstrated a strong correlation to beach properties, remaining low at exposed beaches but increasing sharply in more sheltered conditions. β-diversity did not correlate with beach properties for either diatoms or ciliates. We suggest that wave action and sediment properties are the main drivers controlling the diversity and composition of the intertidal microbenthos. Diatoms and ciliates, however, demonstrated divergent response to these factors. Epipelic and epipsammic diatoms exhibited 2 different strategies to adapt to their environments and therefore were complementarily distributed along the environmental gradient and compensated for each other in diversity. Most ciliates demonstrated a similar mode of habitat selection but differed in their degree of tolerance. Euryporal (including mesoporal) species were relatively tolerant to wave action and therefore occurred under a wide range of beach conditions, though their abundance and diversity were highest in fine, relatively stable sediments on sheltered beaches, whereas the specific interstitial (i.e. genuine microporal) species were mostly restricted to only these habitats.

scholarly journals Predictive modelling of soils’ hydraulic conductivity using artificial neural network and multiple linear regression

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Charles Gbenga Williams ◽  
Oluwapelumi O. Ojuri
Keyword(s):  
Neural Network ◽  
Artificial Neural Network ◽  
Hydraulic Conductivity ◽  
Linear Regression ◽  
Multiple Linear Regression ◽  
Coarse Grained ◽  
Soil Types ◽  
Wide Range ◽  
Artificial Neural ◽  
Input Variables

AbstractAs a result of heterogeneity nature of soils and variation in its hydraulic conductivity over several orders of magnitude for various soil types from fine-grained to coarse-grained soils, predictive methods to estimate hydraulic conductivity of soils from properties considered more easily obtainable have now been given an appropriate consideration. This study evaluates the performance of artificial neural network (ANN) being one of the popular computational intelligence techniques in predicting hydraulic conductivity of wide range of soil types and compared with the traditional multiple linear regression (MLR). ANN and MLR models were developed using six input variables. Results revealed that only three input variables were statistically significant in MLR model development. Performance evaluations of the developed models using determination coefficient and mean square error show that the prediction capability of ANN is far better than MLR. In addition, comparative study with available existing models shows that the developed ANN and MLR in this study performed relatively better.

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