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Publications in Natural Sciences by NOMIS researchers

Protein compactness and interaction valency define the architecture of a biomolecular condensate across scales

NOMIS Researcher(s)

Published in

July 20, 2023

Non-membrane-bound biomolecular condensates have been proposed to represent an important mode of subcellular organization in diverse biological settings. However, the fundamental principles governing the spatial organization and dynamics of condensates at the atomistic level remain unclear. The Saccharomyces cerevisiae Lge1 protein is required for histone H2B ubiquitination and its N-terminal intrinsically disordered fragment (Lge11-80) undergoes robust phase separation. This study connects single-and multi-chain all-atom molecular dynamics simulations of Lge11-80 with the in vitro behavior of Lge11-80 condensates. Analysis of modeled protein-protein interactions elucidates the key determinants of Lge11-80 condensate formation and links configurational entropy, valency, and compactness of proteins inside the condensates. A newly derived analytical formalism, related to colloid fractal cluster formation, describes condensate architecture across length scales as a function of protein valency and compactness. In particular, the formalism provides an atomisti-cally resolved model of Lge11-80 condensates on the scale of hundreds of nanometers starting from individual protein conformers captured in simulations. The simulation-derived fractal dimensions of condensates of Lge11-80 and its mutants agree with their in vitro morphologies. The presented framework enables a multiscale description of biomolecular condensates and embeds their study in a wider context of colloid self-organization. © Polyansky, Gallego et al.

Research field(s)
Natural Sciences

DOI
10.7554/eLife.80038

Inductively shunted transmons exhibit noise insensitive plasmon states and a fluxon decay exceeding 3 hours

NOMIS Researcher(s)

Published in

July 5, 2023

Currently available quantum processors are dominated by noise, which severely limits their applicability and motivates the search for new physical qubit encodings. In this work, we introduce the inductively shunted transmon, a weakly flux-tunable superconducting qubit that offers charge offset protection for all levels and a 20-fold reduction in flux dispersion compared to the state-of-the-art resulting in a constant coherence over a full flux quantum. The parabolic confinement provided by the inductive shunt as well as the linearity of the geometric superinductor facilitates a high-power readout that resolves quantum jumps with a fidelity and QND-ness of >90% and without the need for a Josephson parametric amplifier. Moreover, the device reveals quantum tunneling physics between the two prepared fluxon ground states with a measured average decay time of up to 3.5 h. In the future, fast time-domain control of the transition matrix elements could offer a new path forward to also achieve full qubit control in the decay-protected fluxon basis. © 2023, The Author(s).

Research field(s)
Natural Sciences, Physics & Astronomy, General Physics

DOI
10.1038/s41467-023-39656-2

X-ray Thomson scattering spectra from density functional theory molecular dynamics simulations based on a modified Chihara formula

NOMIS Researcher(s)

Published in

June 14, 2023

We study ab initio approaches for calculating x-ray Thomson scattering spectra from density functional theory molecular dynamics simulations based on a modified Chihara formula that expresses the inelastic contribution in terms of the dielectric function. We study the electronic dynamic structure factor computed from the Mermin dielectric function using an ab initio electron-ion collision frequency in comparison to computations using a linear-response time-dependent density functional theory (LR-TDDFT) framework for hydrogen and beryllium and investigate the dispersion of free-free and bound-free contributions to the scattering signal. A separate treatment of these contributions, where only the free-free part follows the Mermin dispersion, shows good agreement with LR-TDDFT results for ambient-density beryllium, but breaks down for highly compressed matter where the bound states become pressure ionized. LR-TDDFT is used to reanalyze x-ray Thomson scattering experiments on beryllium demonstrating strong deviations from the plasma conditions inferred with traditional analytic models at small scattering angles. © 2023 American Physical Society.

Research field(s)
Natural Sciences, Physics & Astronomy, Fluids & Plasmas

DOI
10.1103/PhysRevE.107.065207

Melting curve of superionic ammonia at planetary interior conditions

NOMIS Researcher(s)

Published in

May 29, 2023

Under high pressures and temperatures, molecular systems with substantial polarization charges, such as ammonia and water, are predicted to form superionic phases and dense fluid states with dissociating molecules and high electrical conductivity. This behaviour potentially plays a role in explaining the origin of the multipolar magnetic fields of Uranus and Neptune, whose mantles are thought to result from a mixture of H2O, NH3 and CH4 ices. Determining the stability domain, melting curve and electrical conductivity of these superionic phases is therefore crucial for modelling planetary interiors and dynamos. Here we report the melting curve of superionic ammonia up to 300 GPa from laser-driven shock compression of pre-compressed samples and atomistic calculations. We show that ammonia melts at lower temperatures than water above 100 GPa and that fluid ammonia’s electrical conductivity exceeds that of water at conditions predicted by hot, super-adiabatic models for Uranus and Neptune, and enhances the conductivity in their fluid water-rich dynamo layers. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

Research field(s)
Natural Sciences, Physics & Astronomy, Fluids & Plasmas

DOI
10.1038/s41567-023-02074-8

Tunable directional photon scattering from a pair of superconducting qubits

NOMIS Researcher(s)

Published in

May 24, 2023

The ability to control the direction of scattered light is crucial to provide flexibility and scalability for a wide range of on-chip applications, such as integrated photonics, quantum information processing, and nonlinear optics. Tunable directionality can be achieved by applying external magnetic fields that modify optical selection rules, by using nonlinear effects, or interactions with vibrations. However, these approaches are less suitable to control microwave photon propagation inside integrated superconducting quantum devices. Here, we demonstrate on-demand tunable directional scattering based on two periodically modulated transmon qubits coupled to a transmission line at a fixed distance. By changing the relative phase between the modulation tones, we realize unidirectional forward or backward photon scattering. Such an in-situ switchable mirror represents a versatile tool for intra- and inter-chip microwave photonic processors. In the future, a lattice of qubits can be used to realize topological circuits that exhibit strong nonreciprocity or chirality. © 2023, The Author(s).

Research field(s)
Natural Sciences, Physics & Astronomy, Optics

DOI
h10.1038/s41467-023-38761-6

Imputing missing data in plant traits: A guide to improve gap-filling

NOMIS Researcher(s)

Published in

May 16, 2023

Aim: Globally distributed plant trait data are increasingly used to understand relationships between biodiversity and ecosystem processes. However, global trait databases are sparse because they are compiled from many, mostly small databases. This sparsity in both trait space completeness and geographical distribution limits the potential for both multivariate and global analyses. Thus, ‘gap-filling’ approaches are often used to impute missing trait data. Recent methods, like Bayesian hierarchical probabilistic matrix factorization (BHPMF), can impute large and sparse data sets using side information. We investigate whether BHPMF imputation leads to biases in trait space and identify aspects influencing bias to provide guidance for its usage. Innovation: We use a fully observed trait data set from which entries are randomly removed, along with extensive but sparse additional data. We use BHPMF for imputation and evaluate bias by: (1) accuracy (residuals, RMSE, trait means), (2) correlations (bi- and multivariate) and (3) taxonomic and functional clustering (valuewise, uni- and multivariate). BHPMF preserves general patterns of trait distributions but induces taxonomic clustering. Data set–external trait data had little effect on induced taxonomic clustering and stabilized trait–trait correlations. Main Conclusions: Our study extends the criteria for the evaluation of gap-filling beyond RMSE, providing insight into statistical data structure and allowing better informed use of imputed trait data, with improved practice for imputation. We expect our findings to be valuable beyond applications in plant ecology, for any study using hierarchical side information for imputation. © 2023 The Authors. Global Ecology and Biogeography published by John Wiley & Sons Ltd.

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1111/geb.13695

A Tropical Cocktail of Organic Matter Sources: Variability in Supraglacial and Glacier Outflow Dissolved Organic Matter Composition and Age Across the Ecuadorian Andes

NOMIS Researcher(s)

Published in

May 9, 2023

The biogeochemistry of rapidly retreating Andean glaciers is poorly understood, and Ecuadorian glacier dissolved organic matter (DOM) composition is unknown. This study examined molecular composition and carbon isotopes of DOM from supraglacial and outflow streams (n = 5 and 14, respectively) across five ice capped volcanoes in Ecuador. Compositional metrics were paired with streamwater isotope analyses (δ18O) to assess if outflow DOM composition was associated with regional precipitation gradients and thus an atmospheric origin of glacier DOM. Ecuadorian glacier outflows exported ancient, biolabile dissolved organic carbon (DOC), and DOM contained a high relative abundance (RA) of aliphatic and peptide-like compounds (≥27%RA). Outflows were consistently more depleted in Δ14C-DOC (i.e., older) compared to supraglacial streams (mean −195.2 and −61.3‰ respectively), perhaps due to integration of spatially heterogenous and variably aged DOM pools across the supraglacial environment, or incorporation of aged subglacial OM as runoff was routed to the outflow. Across Ecuador, Δ14C-DOC enrichment was associated with decreased aromaticity of DOM, due to increased contributions of organic matter (OM) from microbial processes or atmospheric deposition of recently fixed and subsequently degraded OM (e.g., biomass burning byproducts). There was a regional gradient between glacier outflow DOM composition and streamwater δ18O, suggesting covariation between regional precipitation gradients and the DOM exported from glacier outflows. Ultimately, this highlights that atmospheric deposition may exert a control on glacier outflow DOM composition, suggesting regional air circulation patterns and precipitation sources in part determine the origins and quality of OM exported from glacier environments. © 2023. American Geophysical Union. All Rights Reserved.

Research field(s)
Natural Sciences, Earth & Environmental Sciences, Meteorology & Atmospheric Sciences

DOI
10.1029/2022JG007188

Ab initio calculation of the reflectivity of molecular fluids under shock compression

NOMIS Researcher(s)

Published in

April 13, 2023

We calculate reflectivities of dynamically compressed water, water-ethanol mixtures, and ammonia at infrared and optical wavelengths with density functional theory and molecular dynamics simulations. The influence of the exchange-correlation functional on the results is examined in detail. Our findings indicate that the consistent use of the HSE hybrid functional reproduces experimental results much better than the commonly used PBE functional. The HSE functional offers not only a more accurate description of the electronic band gap but also shifts the onset of molecular dissociation in the molecular dynamics simulations to significantly higher pressures. We also highlight the importance of using accurate reference standards in reflectivity experiments and reanalyze infrared and optical reflectivity data from recent experiments. Thus, our combined theoretical and experimental work explains and resolves lingering discrepancies between calculations and measurements for the investigated molecular substances under shock compression. © 2023 American Physical Society.

Research field(s)
Natural Sciences

DOI
10.1103/PhysRevB.107.134109

Curvature induces active velocity waves in rotating spherical tissues

NOMIS Researcher(s)

Published in

March 24, 2023

The multicellular organization of diverse systems, including embryos, intestines, and tumors relies on coordinated cell migration in curved environments. In these settings, cells establish supracellular patterns of motion, including collective rotation and invasion. While such collective modes have been studied extensively in flat systems, the consequences of geometrical and topological constraints on collective migration in curved systems are largely unknown. Here, we discover a collective mode of cell migration in rotating spherical tissues manifesting as a propagating single-wavelength velocity wave. This wave is accompanied by an apparently incompressible supracellular flow pattern featuring topological defects as dictated by the spherical topology. Using a minimal active particle model, we reveal that this collective mode arises from the effect of curvature on the active flocking behavior of a cell layer confined to a spherical surface. Our results thus identify curvature-induced velocity waves as a mode of collective cell migration, impacting the dynamical organization of 3D curved tissues. © 2023, The Author(s).

Research field(s)
Natural Sciences, Physics & Astronomy, Fluids & Plasmas

DOI
10.1038/s41467-023-37054-2

Thermodynamics of diamond formation from hydrocarbon mixtures in planets

NOMIS Researcher(s)

Published in

February 27, 2023

Hydrocarbon mixtures are extremely abundant in the Universe, and diamond formation from them can play a crucial role in shaping the interior structure and evolution of planets. With first-principles accuracy, we first estimate the melting line of diamond, and then reveal the nature of chemical bonding in hydrocarbons at extreme conditions. We finally establish the pressure-temperature phase boundary where it is thermodynamically possible for diamond to form from hydrocarbon mixtures with different atomic fractions of carbon. Notably, here we show a depletion zone at pressures above 200 GPa and temperatures below 3000 K-3500 K where diamond formation is thermodynamically favorable regardless of the carbon atomic fraction, due to a phase separation mechanism. The cooler condition of the interior of Neptune compared to Uranus means that the former is much more likely to contain the depletion zone. Our findings can help explain the dichotomy of the two ice giants manifested by the low luminosity of Uranus, and lead to a better understanding of (exo-)planetary formation and evolution. © 2023, The Author(s).

Research field(s)
Natural Sciences, Physics & Astronomy, Fluids & Plasmas

DOI
10.1038/s41467-023-36841-1

River ecosystem metabolism and carbon biogeochemistry in a changing world

NOMIS Researcher(s)

Published in

January 18, 2023

River networks represent the largest biogeochemical nexus between the continents, ocean and atmosphere. Our current understanding of the role of rivers in the global carbon cycle remains limited, which makes it difficult to predict how global change may alter the timing and spatial distribution of riverine carbon sequestration and greenhouse gas emissions. Here we review the state of river ecosystem metabolism research and synthesize the current best available estimates of river ecosystem metabolism. We quantify the organic and inorganic carbon flux from land to global rivers and show that their net ecosystem production and carbon dioxide emissions shift the organic to inorganic carbon balance en route from land to the coastal ocean. Furthermore, we discuss how global change may affect river ecosystem metabolism and related carbon fluxes and identify research directions that can help to develop better predictions of the effects of global change on riverine ecosystem processes. We argue that a global river observing system will play a key role in understanding river networks and their future evolution in the context of the global carbon budget. © 2023, Springer Nature Limited.

Research field(s)
Natural Sciences, Earth & Environmental Sciences, Meteorology & Atmospheric Sciences

DOI
10.1038/s41586-022-05500-8

Tropical forests post-logging are a persistent net carbon source to the atmosphere

NOMIS Researcher(s)

Published in

January 9, 2023

Logged and structurally degraded tropical forests are fast becoming one of the most prevalent land-use types throughout the tropics and are routinely assumed to be a net carbon sink because they experience rapid rates of tree regrowth. Yet this assumption is based on forest biomass inventories that record carbon stock recovery but fail to account for the simultaneous losses of carbon from soil and necromass. Here, we used forest plots and an eddy covariance tower to quantify and partition net ecosystem CO2 exchange in Malaysian Borneo, a region that is a hot spot for deforestation and forest degradation. Our data represent the complete carbon budget for tropical forests measured throughout a logging event and subsequent recovery and found that they constitute a substantial and persistent net carbon source. Consistent with existing literature, our study showed a significantly greater woody biomass gain across moderately and heavily logged forests compared with unlogged forests, but this was counteracted by much larger carbon losses from soil organic matter and deadwood in logged forests. We estimate an average carbon source of 1.75 ± 0.94 Mg C ha−1 yr−1 within moderately logged plots and 5.23 ± 1.23 Mg C ha−1 yr−1 in unsustainably logged and severely degraded plots, with emissions continuing at these rates for at least one-decade post-logging. Our data directly contradict the default assumption that recovering logged and degraded tropical forests are net carbon sinks, implying the amount of carbon being sequestered across the world’s tropical forests may be considerably lower than currently estimated. Copyright © 2023 the Author(s).

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1073/pnas.2214462120

Logged tropical forests have amplified and diverse ecosystem energetics

NOMIS Researcher(s)

Published in

December 22, 2022

Old-growth tropical forests are widely recognized as being immensely important for their biodiversity and high biomass1. Conversely, logged tropical forests are usually characterized as degraded ecosystems2. However, whether logging results in a degradation in ecosystem functions is less clear: shifts in the strength and resilience of key ecosystem processes in large suites of species have rarely been assessed in an ecologically integrated and quantitative framework. Here we adopt an ecosystem energetics lens to gain new insight into the impacts of tropical forest disturbance on a key integrative aspect of ecological function: food pathways and community structure of birds and mammals. We focus on a gradient spanning old-growth and logged forests and oil palm plantations in Borneo. In logged forest there is a 2.5-fold increase in total resource consumption by both birds and mammals compared to that in old-growth forests, probably driven by greater resource accessibility and vegetation palatability. Most principal energetic pathways maintain high species diversity and redundancy, implying maintained resilience. Conversion of logged forest into oil palm plantation results in the collapse of most energetic pathways. Far from being degraded ecosystems, even heavily logged forests can be vibrant and diverse ecosystems with enhanced levels of ecological function.

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1038/s41586-022-05523-1

Majorana-like Coulomb spectroscopy in the absence of zero-bias peaks

NOMIS Researcher(s)

Published in

December 15, 2022

Hybrid semiconductor–superconductor devices hold great promise for realizing topological quantum computing with Majorana zero modes1–5. However, multiple claims of Majorana detection, based on either tunnelling6–10 or Coulomb blockade (CB) spectroscopy11,12, remain disputed. Here we devise an experimental protocol that allows us to perform both types of measurement on the same hybrid island by adjusting its charging energy via tunable junctions to the normal leads. This method reduces ambiguities of Majorana detections by checking the consistency between CB spectroscopy and zero-bias peaks in non-blockaded transport. Specifically, we observe junction-dependent, even–odd modulated, single-electron CB peaks in InAs/Al hybrid nanowires without concomitant low-bias peaks in tunnelling spectroscopy. We provide a theoretical interpretation of the experimental observations in terms of low-energy, longitudinally confined island states rather than overlapping Majorana modes. Our results highlight the importance of combined measurements on the same device for the identification of topological Majorana zero modes.

Research field(s)
Natural Sciences, Physics & Astronomy, Applied Physics

DOI
10.1038/s41586-022-05382-w

A novel synthesis of two decades of microsatellite studies on European beech reveals decreasing genetic diversity from glacial refugia

NOMIS Researcher(s)

Published in

December 12, 2022

Genetic diversity influences the evolutionary potential of forest trees under changing environmental conditions, thus indirectly the ecosystem services that forests provide. European beech (Fagus sylvatica L.) is a dominant European forest tree species that increasingly suffers from climate change-related die-back. Here, we conducted a systematic literature review of neutral genetic diversity in European beech and created a meta-data set of expected heterozygosity (He) from all past studies providing nuclear microsatellite data. We propose a novel approach, based on population genetic theory and a min–max scaling to make past studies comparable. Using a new microsatellite data set with unprecedented geographic coverage and various re-sampling schemes to mimic common sampling biases, we show the potential and limitations of the scaling approach. The scaled meta-dataset reveals the expected trend of decreasing genetic diversity from glacial refugia across the species range and also supports the hypothesis that different lineages met and admixed north of the European mountain ranges. As a result, we present a map of genetic diversity across the range of European beech which could help to identify seed source populations harboring greater diversity and guide sampling strategies for future genome-wide and functional investigations of genetic variation. Our approach illustrates how to combine information from several nuclear microsatellite data sets to describe patterns of genetic diversity extending beyond the geographic scale or mean number of loci used in each individual study, and thus is a proof-of-concept for synthesizing knowledge from existing studies also in other species. © 2022, The Author(s).

Research field(s)
Natural Sciences

DOI
10.1007/s11295-022-01577-4

The ABCs of relational values: Environmental values that include aspects of both intrinsic and instrumental valuing

NOMIS Researcher(s)

Published in

December 1, 2022

In this paper we suggest an interpretation of the concept of ‘relational value’ that could be useful in both environmental ethics and empirical analyses. We argue that relational valuing includes aspects of intrinsic and instrumental valuing. If relational values are attributed, objects are appreciated because the relationship with them contributes to the human flourishing component of well-being (instrumental aspect). At the same time, attributing relational value involves genuine esteem for the valued item (intrinsic aspect). We also introduce the notions of mediating and indirect relational environmental values, attributed in relationships involving people as well as environmental objects. We close by proposing how our analysis can be used in empirical research.

Research field(s)
Natural Sciences, Earth & Environmental Sciences, Environmental Sciences

DOI
10.3197/096327120X15973379803726

Respecting the Nonhuman Other: Individual Natural Otherness and the Case for Incommensurability of Moral Standing

NOMIS Researcher(s)

Published in

December 1, 2022

The concept of natural otherness can be found throughout the environmental ethics literature. Drawing on this concept, this article pursues two aims. For one, it argues for an account of individual natural otherness as stable difference as opposed to accounts of natural otherness that put more emphasis on inde-pendence for the purpose of differentiating individual natural otherness from the concept of wildness. Secondly, this account of natural otherness is engaged to argue for a particular way of theorising the moral standing of individual nonhuman entities. While individual natural otherness in itself does not pro-vide an account of whether an entity matters morally in itself (that is, whether it is morally considerable); it points to an account of incommensurable moral significance for all entities which are attributed moral considerability. That is an often-overlooked alternative to egalitarian or hierarchical accounts of moral significance. Individual natural otherness understood in this way in turn pro-vides another explanatory story for why relational accounts of environmental ethics that strongly emphasise the importance of concepts such as wildness are particularly salient.

Research field(s)
Natural Sciences, Earth & Environmental Sciences, Environmental Sciences

DOI
10.3197/096327121X16328186623913

Downstream Effects of Mutations in SOD1 and TARDBP Converge on Gene Expression Impairment in Patient-Derived Motor Neurons

NOMIS Researcher(s)

Published in

September 1, 2022

Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease marked by death of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Despite extensive research, the reason for neurodegeneration is still not understood. To generate novel hypotheses of putative underlying molecular mechanisms, we used human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls to perform high-throughput RNA-sequencing (RNA-Seq). An integrated bioinformatics approach was employed to identify differentially expressed genes (DEGs) and key pathways underlying these familial forms of the disease (fALS). In TDP43-ALS, we found dysregulation of transcripts encoding components of the transcriptional machinery and transcripts involved in splicing regulation were particularly affected. In contrast, less is known about the role of SOD1 in RNA metabolism in motor neurons. Here, we found that many transcripts relevant for mitochondrial function were specifically altered in SOD1-ALS, indicating that transcriptional signatures and expression patterns can vary significantly depending on the causal gene that is mutated. Surprisingly, however, we identified a clear downregulation of genes involved in protein translation in SOD1-ALS suggesting that ALS-causing SOD1 mutations shift cellular RNA abundance profiles to cause neural dysfunction. Altogether, we provided here an extensive profiling of mRNA expression in two ALS models at the cellular level, corroborating the major role of RNA metabolism and gene expression as a common pathomechanism in ALS.

Research field(s)
Natural Sciences, Physics & Astronomy, Chemical Physics

DOI
10.3390/ijms23179652

Effects of boundary layer thickness on the estimation of equivalent sandgrain roughness in zero-pressure-gradient boundary layers

NOMIS Researcher(s)

Published in

August 1, 2022

Experiments were conducted in zero-pressure-gradient boundary layers over a rough surface. Profiles of mean velocity and turbulence quantities were acquired using laser Doppler velocimetry at twelve streamwise locations for each of three different freestream velocities. Momentum thickness Reynolds numbers ranged from 1550 to 13,650. The roughness was stochastic with positive skewness, and the ratio of the boundary layer thickness, δ, to the root-mean-square roughness height varied from 55 to 141. The equivalent sandgrain roughness height, ks, was approximately 4 times the rms roughness height. In the outer region of the boundary layer, the mean velocity and turbulence results were found to be invariant with Reynolds number and δ, when scaled using δ and the friction velocity. The outer region quantities exhibited similarity with equivalent smooth-wall boundary layer quantities, in agreement with results from the literature. The equivalent sandgrain roughness was computed from the mean velocity results using a standard correlation, and was found to vary noticeably and inversely with δ when δ/ks was less than about 40. The possible existence of a modified correlation to account for the δ/ks dependence was discussed. Such a correlation might prove useful for extracting ks values from low δ/ks data and for predicting the effect of roughness with a known ks on boundary layers with varying δ/ks. Graphical abstract: [Figure not available: see fulltext.]

Research field(s)
Natural Sciences, Physics & Astronomy, Fluids & Plasmas

DOI
10.1007/s00348-022-03479-6

Phase-separating RNA-binding proteins form heterogeneous distributions of clusters in subsaturated solutions

NOMIS Researcher(s)

Published in

July 12, 2022

Macromolecular phase separation is thought to be one of the processes that drives the formation of membraneless biomolecular condensates in cells. The dynamics of phase separation are thought to follow the tenets of classical nucleation theory, and, therefore, subsaturated solutions should be devoid of clusters with more than a few molecules. We tested this prediction using in vitro biophysical studies to characterize subsaturated solutions of phase-separating RNA-binding proteins with intrinsically disordered prion-like domains and RNA-binding domains. Surprisingly, and in direct contradiction to expectations from classical nucleation theory, we find that subsaturated solutions are characterized by the presence of heterogeneous distributions of clusters. The distributions of cluster sizes, which are dominated by small species, shift continuously toward larger sizes as protein concentrations increase and approach the saturation concentration. As a result, many of the clusters encompass tens to hundreds of molecules, while less than 1% of the solutions are mesoscale species that are several hundred nanometers in diameter. We find that cluster formation in subsaturated solutions and phase separation in supersaturated solutions are strongly coupled via sequence-encoded interactions. We also find that cluster formation and phase separation can be decoupled using solutes as well as specific sets of mutations. Our findings, which are concordant with predictions for associative polymers, implicate an interplay between networks of sequence-specific and solubility-determining interactions that, respectively, govern cluster formation in subsaturated solutions and the saturation concentrations above which phase separation occurs.

Research field(s)
Natural Sciences, Physics & Astronomy, Chemical Physics

DOI
10.1073/pnas.2202222119

Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration

NOMIS Researcher(s)

Published in

July 1, 2022

Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.

Research field(s)
Natural Sciences, Physics & Astronomy, General Physics

DOI
10.1103/PhysRevX.12.031041

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