More Like this

1. Simulations of dynamically cross-linked actin networks: Morphology, rheology, and hydrodynamic interactions

   https://doi.org/10.1371/journal.pcbi.1009240  

   Maxian, Ondrej ; Peláez, Raúl P. ; Mogilner, Alex ; Donev, Aleksandar ( December 2021 , PLOS Computational Biology)

   Merks, Roeland M.H. (Ed.)

   Cross-linked actin networks are the primary component of the cell cytoskeleton and have been the subject of numerous experimental and modeling studies. While these studies have demonstrated that the networks are viscoelastic materials, evolving from elastic solids on short timescales to viscous fluids on long ones, questions remain about the duration of each asymptotic regime, the role of the surrounding fluid, and the behavior of the networks on intermediate timescales. Here we perform detailed simulations of passively cross-linked non-Brownian actin networks to quantify the principal timescales involved in the elastoviscous behavior, study the role of nonlocal hydrodynamic interactions, and parameterize continuum models from discrete stochastic simulations. To do this, we extend our recent computational framework for semiflexible filament suspensions, which is based on nonlocal slender body theory, to actin networks with dynamic cross linkers and finite filament lifetime. We introduce a model where the cross linkers are elastic springs with sticky ends stochastically binding to and unbinding from the elastic filaments, which randomly turn over at a characteristic rate. We show that, depending on the parameters, the network evolves to a steady state morphology that is either an isotropic actin mesh or a mesh with embedded actin bundles. For different degrees of bundling, we numerically apply small-amplitude oscillatory shear deformation to extract three timescales from networks of hundreds of filaments and cross linkers. We analyze the dependence of these timescales, which range from the order of hundredths of a second to the actin turnover time of several seconds, on the dynamic nature of the links, solvent viscosity, and filament bending stiffness. We show that the network is mostly elastic on the short time scale, with the elasticity coming mainly from the cross links, and viscous on the long time scale, with the effective viscosity originating primarily from stretching and breaking of the cross links. We show that the influence of nonlocal hydrodynamic interactions depends on the network morphology: for homogeneous meshworks, nonlocal hydrodynamics gives only a small correction to the viscous behavior, but for bundled networks it both hinders the formation of bundles and significantly lowers the resistance to shear once bundles are formed. We use our results to construct three-timescale generalized Maxwell models of the networks. 

   more » « less
2. The Abell 3391/95 galaxy cluster system: A 15 Mpc intergalactic medium emission filament, a warm gas bridge, infalling matter clumps, and (re-) accelerated plasma discovered by combining SRG/eROSITA data with ASKAP/EMU and DECam data

   https://doi.org/10.1051/0004-6361/202039590  

   Reiprich, T. H. ; Veronica, A. ; Pacaud, F. ; Ramos-Ceja, M. E. ; Ota, N. ; Sanders, J. ; Kara, M. ; Erben, T. ; Klein, M. ; Erler, J. ; et al ( March 2021 , Astronomy & Astrophysics)

   null (Ed.)

   Context. Inferences about dark matter, dark energy, and the missing baryons all depend on the accuracy of our model of large-scale structure evolution. In particular, with cosmological simulations in our model of the Universe, we trace the growth of structure, and visualize the build-up of bigger structures from smaller ones and of gaseous filaments connecting galaxy clusters. Aims. Here we aim to reveal the complexity of the large-scale structure assembly process in great detail and on scales from tens of kiloparsecs up to more than 10 Mpc with new sensitive large-scale observations from the latest generation of instruments. We also aim to compare our findings with expectations from our cosmological model. Methods. We used dedicated SRG/eROSITA performance verification (PV) X-ray, ASKAP/EMU Early Science radio, and DECam optical observations of a ~15 deg 2 region around the nearby interacting galaxy cluster system A3391/95 to study the warm-hot gas in cluster outskirts and filaments, the surrounding large-scale structure and its formation process, the morphological complexity in the inner parts of the clusters, and the (re-)acceleration of plasma. We also used complementary Sunyaev-Zeldovich (SZ) effect data from the Planck survey and custom-made Galactic total (neutral plus molecular) hydrogen column density maps based on the HI4PI and IRAS surveys. We relate the observations to expectations from cosmological hydrodynamic simulations from the Magneticum suite. Results. We trace the irregular morphology of warm and hot gas of the main clusters from their centers out to well beyond their characteristic radii, r 200 . Between the two main cluster systems, we observe an emission bridge on large scale and with good spatial resolution. This bridge includes a known galaxy group but this can only partially explain the emission. Most gas in the bridge appears hot, but thanks to eROSITA’s unique soft response and large field of view, we discover some tantalizing hints for warm, truly primordial filamentary gas connecting the clusters. Several matter clumps physically surrounding the system are detected. For the “Northern Clump,” we provide evidence that it is falling towards A3391 from the X-ray hot gas morphology and radio lobe structure of its central AGN. Moreover, the shapes of these X-ray and radio structures appear to be formed by gas well beyond the virial radius, r 100 , of A3391, thereby providing an indirect way of probing the gas in this elusive environment. Many of the extended sources in the field detected by eROSITA are also known clusters or new clusters in the background, including a known SZ cluster at redshift z = 1. We find roughly an order of magnitude more cluster candidates than the SPT and ACT surveys together in the same area. We discover an emission filament north of the virial radius of A3391 connecting to the Northern Clump. Furthermore, the absorption-corrected eROSITA surface brightness map shows that this emission filament extends south of A3395 and beyond an extended X-ray-emitting object (the “Little Southern Clump”) towards another galaxy cluster, all at the same redshift. The total projected length of this continuous warm-hot emission filament is 15 Mpc, running almost 4 degrees across the entire eROSITA PV observation field. The Northern and Southern Filament are each detected at >4 σ . The Planck SZ map additionally appears to support the presence of both new filaments. Furthermore, the DECam galaxy density map shows galaxy overdensities in the same regions. Overall, the new datasets provide impressive confirmation of the theoretically expected structure formation processes on the individual system level, including the surrounding warm-hot intergalactic medium distribution; the similarities of features found in a similar system in the Magneticum simulation are striking. Our spatially resolved findings show that baryons indeed reside in large-scale warm-hot gas filaments with a clumpy structure. 

   more » « less
3. Neural representations of cryo-EM maps and a graph-based interpretation

   https://doi.org/10.1186/s12859-022-04942-1  

   Ranno, Nathan ; Si, Dong ( September 2022 , BMC Bioinformatics)

   Advances in imagery at atomic and near-atomic resolution, such as cryogenic electron microscopy (cryo-EM), have led to an influx of high resolution images of proteins and other macromolecular structures to data banks worldwide. Producing a protein structure from the discrete voxel grid data of cryo-EM maps involves interpolation into the continuous spatial domain. We present a novel data format called the neural cryo-EM map, which is formed from a set of neural networks that accurately parameterize cryo-EM maps and provide native, spatially continuous data for density and gradient. As a case study of this data format, we create graph-based interpretations of high resolution experimental cryo-EM maps.

   Normalized cryo-EM map values interpolated using the non-linear neural cryo-EM format are more accurate, consistently scoring less than 0.01 mean absolute error, than a conventional tri-linear interpolation, which scores up to 0.12 mean absolute error. Our graph-based interpretations of 115 experimental cryo-EM maps from 1.15 to 4.0 Å resolution provide high coverage of the underlying amino acid residue locations, while accuracy of nodes is correlated with resolution. The nodes of graphs created from atomic resolution maps (higher than 1.6 Å) provide greater than 99% residue coverage as well as 85% full atomic coverage with a mean of 0.19 Å root mean squared deviation. Other graphs have a mean 84% residue coverage with less specificity of the nodes due to experimental noise and differences of density context at lower resolutions.

   The fully continuous and differentiable nature of the neural cryo-EM map enables the adaptation of the voxel data to alternative data formats, such as a graph that characterizes the atomic locations of the underlying protein or macromolecular structure. Graphs created from atomic resolution maps are superior in finding atom locations and may serve as input to predictive residue classification and structure segmentation methods. This work may be generalized to transform any 3D grid-based data format into non-linear, continuous, and differentiable format for downstream geometric deep learning applications.

    

   more » « less
4. A unified framework for packing deformable and non-deformable subcellular structures in crowded cryo-electron tomogram simulation

   https://doi.org/10.1186/s12859-020-03660-w  

   Liu, Sinuo ; Ban, Xiaojuan ; Zeng, Xiangrui ; Zhao, Fengnian ; Gao, Yuan ; Wu, Wenjie ; Zhang, Hongpan ; Chen, Feiyang ; Hall, Thomas ; Gao, Xin ; et al ( December 2020 , BMC Bioinformatics)

   null (Ed.)

   Abstract Background Cryo-electron tomography is an important and powerful technique to explore the structure, abundance, and location of ultrastructure in a near-native state. It contains detailed information of all macromolecular complexes in a sample cell. However, due to the compact and crowded status, the missing edge effect, and low signal to noise ratio (SNR), it is extremely challenging to recover such information with existing image processing methods. Cryo-electron tomogram simulation is an effective solution to test and optimize the performance of the above image processing methods. The simulated images could be regarded as the labeled data which covers a wide range of macromolecular complexes and ultrastructure. To approximate the crowded cellular environment, it is very important to pack these heterogeneous structures as tightly as possible. Besides, simulating non-deformable and deformable components under a unified framework also need to be achieved. Result In this paper, we proposed a unified framework for simulating crowded cryo-electron tomogram images including non-deformable macromolecular complexes and deformable ultrastructures. A macromolecule was approximated using multiple balls with fixed relative positions to reduce the vacuum volume. A ultrastructure, such as membrane and filament, was approximated using multiple balls with flexible relative positions so that this structure could deform under force field. In the experiment, 400 macromolecules of 20 representative types were packed into simulated cytoplasm by our framework, and numerical verification proved that our method has a smaller volume and higher compression ratio than the baseline single-ball model. We also packed filaments, membranes and macromolecules together, to obtain a simulated cryo-electron tomogram image with deformable structures. The simulated results are closer to the real Cryo-ET, making the analysis more difficult. The DOG particle picking method and the image segmentation method are tested on our simulation data, and the experimental results show that these methods still have much room for improvement. Conclusion The proposed multi-ball model can achieve more crowded packaging results and contains richer elements with different properties to obtain more realistic cryo-electron tomogram simulation. This enables users to simulate cryo-electron tomogram images with non-deformable macromolecular complexes and deformable ultrastructures under a unified framework. To illustrate the advantages of our framework in improving the compression ratio, we calculated the volume of simulated macromolecular under our multi-ball method and traditional single-ball method. We also performed the packing experiment of filaments and membranes to demonstrate the simulation ability of deformable structures. Our method can be used to do a benchmark by generating large labeled cryo-ET dataset and evaluating existing image processing methods. Since the content of the simulated cryo-ET is more complex and crowded compared with previous ones, it will pose a greater challenge to existing image processing methods. 

   more » « less
5. Generating Chromosome Geometries in a Minimal Cell From Cryo-Electron Tomograms and Chromosome Conformation Capture Maps

   https://doi.org/10.3389/fmolb.2021.644133  

   Gilbert, Benjamin R. ; Thornburg, Zane R. ; Lam, Vinson ; Rashid, Fatema-Zahra M. ; Glass, John I. ; Villa, Elizabeth ; Dame, Remus T. ; Luthey-Schulten, Zaida ( July 2021 , Frontiers in Molecular Biosciences)

   null (Ed.)

   JCVI-syn3A is a genetically minimal bacterial cell, consisting of 493 genes and only a single 543 kbp circular chromosome. Syn3A’s genome and physical size are approximately one-tenth those of the model bacterial organism Escherichia coli ’s, and the corresponding reduction in complexity and scale provides a unique opportunity for whole-cell modeling. Previous work established genome-scale gene essentiality and proteomics data along with its essential metabolic network and a kinetic model of genetic information processing. In addition to that information, whole-cell, spatially-resolved kinetic models require cellular architecture, including spatial distributions of ribosomes and the circular chromosome’s configuration. We reconstruct cellular architectures of Syn3A cells at the single-cell level directly from cryo-electron tomograms, including the ribosome distributions. We present a method of generating self-avoiding circular chromosome configurations in a lattice model with a resolution of 11.8 bp per monomer on a 4 nm cubic lattice. Realizations of the chromosome configurations are constrained by the ribosomes and geometry reconstructed from the tomograms and include DNA loops suggested by experimental chromosome conformation capture (3C) maps. Using ensembles of simulated chromosome configurations we predict chromosome contact maps for Syn3A cells at resolutions of 250 bp and greater and compare them to the experimental maps. Additionally, the spatial distributions of ribosomes and the DNA-crowding resulting from the individual chromosome configurations can be used to identify macromolecular structures formed from ribosomes and DNA, such as polysomes and expressomes. 

   more » « less