@article{10336, abstract = {Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.}, author = {Krausser, Johannes and Knowles, Tuomas P. J. and Šarić, Anđela}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {52}, pages = {33090--33098}, publisher = {National Academy of Sciences}, title = {{Physical mechanisms of amyloid nucleation on fluid membranes}}, doi = {10.1073/pnas.2007694117}, volume = {117}, year = {2020}, } @article{10341, abstract = {Tracing the motion of macromolecules, viruses, and nanoparticles adsorbed onto cell membranes is currently the most direct way of probing the complex dynamic interactions behind vital biological processes, including cell signalling, trafficking, and viral infection. The resulting trajectories are usually consistent with some type of anomalous diffusion, but the molecular origins behind the observed anomalous behaviour are usually not obvious. Here we use coarse-grained molecular dynamics simulations to help identify the physical mechanisms that can give rise to experimentally observed trajectories of nanoscopic objects moving on biological membranes. We find that diffusion on membranes of high fluidities typically results in normal diffusion of the adsorbed nanoparticle, irrespective of the concentration of receptors, receptor clustering, or multivalent interactions between the particle and membrane receptors. Gel-like membranes on the other hand result in anomalous diffusion of the particle, which becomes more pronounced at higher receptor concentrations. This anomalous diffusion is characterised by local particle trapping in the regions of high receptor concentrations and fast hopping between such regions. The normal diffusion is recovered in the limit where the gel membrane is saturated with receptors. We conclude that hindered receptor diffusivity can be a common reason behind the observed anomalous diffusion of viruses, vesicles, and nanoparticles adsorbed on cell and model membranes. Our results enable direct comparison with experiments and offer a new route for interpreting motility experiments on cell membranes.}, author = {Debets, V. E. and Janssen, L. M. C. and Šarić, Anđela}, issn = {1744-683X}, journal = {Soft Matter}, keywords = {condensed matter physics, general chemistry}, number = {47}, pages = {10628--10639}, publisher = {Royal Society of Chemistry}, title = {{Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes}}, doi = {10.1039/d0sm00712a}, volume = {16}, year = {2020}, } @article{10342, abstract = {The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor–related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.}, author = {Tian, Xiaohe and Leite, Diana M. and Scarpa, Edoardo and Nyberg, Sophie and Fullstone, Gavin and Forth, Joe and Matias, Diana and Apriceno, Azzurra and Poma, Alessandro and Duro-Castano, Aroa and Vuyyuru, Manish and Harker-Kirschneck, Lena and Šarić, Anđela and Zhang, Zhongping and Xiang, Pan and Fang, Bin and Tian, Yupeng and Luo, Lei and Rizzello, Loris and Battaglia, Giuseppe}, issn = {2375-2548}, journal = {Science Advances}, keywords = {multidisciplinary}, number = {48}, publisher = {American Association for the Advancement of Science}, title = {{On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias}}, doi = {10.1126/sciadv.abc4397}, volume = {6}, year = {2020}, } @article{10344, abstract = {In this study, we investigate the role of the surface patterning of nanostructures for cell membrane reshaping. To accomplish this, we combine an evolutionary algorithm with coarse-grained molecular dynamics simulations and explore the solution space of ligand patterns on a nanoparticle that promote efficient and reliable cell uptake. Surprisingly, we find that in the regime of low ligand number the best-performing structures are characterized by ligands arranged into long one-dimensional chains that pattern the surface of the particle. We show that these chains of ligands provide particles with high rotational freedom and they lower the free energy barrier for membrane crossing. Our approach reveals a set of nonintuitive design rules that can be used to inform artificial nanoparticle construction and the search for inhibitors of viral entry.}, author = {Forster, Joel C. and Krausser, Johannes and Vuyyuru, Manish R. and Baum, Buzz and Šarić, Anđela}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Exploring the design rules for efficient membrane-reshaping nanostructures}}, doi = {10.1103/physrevlett.125.228101}, volume = {125}, year = {2020}, } @article{10346, abstract = {One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular matrix, where they self-assemble into fibrils of well-defined axial striped patterns. This striped fibrillar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signaling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here, we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril axial pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the striped fibrillar pattern cannot be easily predicted from the interactions between two monomers but is an emergent result of multibody interactions. Our results can help address collagen remodeling in diseases and aging and guide the design of collagen scaffolds for biotechnological applications.}, author = {Hafner, Anne E. and Gyori, Noemi G. and Bench, Ciaran A. and Davis, Luke K. and Šarić, Anđela}, issn = {0006-3495}, journal = {Biophysical Journal}, keywords = {biophysics}, number = {9}, pages = {1791--1799}, publisher = {Cell Press}, title = {{Modeling fibrillogenesis of collagen-mimetic molecules}}, doi = {10.1016/j.bpj.2020.09.013}, volume = {119}, year = {2020}, } @article{10347, abstract = {Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors.}, author = {Michaels, Thomas C. T. and Šarić, Anđela and Meisl, Georg and Heller, Gabriella T. and Curk, Samo and Arosio, Paolo and Linse, Sara and Dobson, Christopher M. and Vendruscolo, Michele and Knowles, Tuomas P. J.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {multidisciplinary}, number = {39}, pages = {24251--24257}, publisher = {National Academy of Sciences}, title = {{Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors}}, doi = {10.1073/pnas.2006684117}, volume = {117}, year = {2020}, } @article{10348, abstract = {The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.}, author = {Pfitzner, Anna-Katharina and Mercier, Vincent and Jiang, Xiuyun and Moser von Filseck, Joachim and Baum, Buzz and Šarić, Anđela and Roux, Aurélien}, issn = {0092-8674}, journal = {Cell}, keywords = {general biochemistry, genetics and molecular biology}, number = {5}, pages = {1140--1155.e18}, publisher = {Elsevier}, title = {{An ESCRT-III polymerization sequence drives membrane deformation and fission}}, doi = {10.1016/j.cell.2020.07.021}, volume = {182}, year = {2020}, } @article{10349, abstract = {Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the transition from the end of one cell cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homolog, CdvB, as a key target of the proteasome and show that its degradation triggers division by allowing constriction of the CdvB1:CdvB2 ESCRT-III division ring. These findings offer a minimal mechanism for ESCRT-III–mediated membrane remodeling and point to a conserved role for the proteasome in eukaryotic and archaeal cell cycle control.}, author = {Tarrason Risa, Gabriel and Hurtig, Fredrik and Bray, Sian and Hafner, Anne E. and Harker-Kirschneck, Lena and Faull, Peter and Davis, Colin and Papatziamou, Dimitra and Mutavchiev, Delyan R. and Fan, Catherine and Meneguello, Leticia and Arashiro Pulschen, Andre and Dey, Gautam and Culley, Siân and Kilkenny, Mairi and Souza, Diorge P. and Pellegrini, Luca and de Bruin, Robertus A. M. and Henriques, Ricardo and Snijders, Ambrosius P. and Šarić, Anđela and Lindås, Ann-Christin and Robinson, Nicholas P. and Baum, Buzz}, issn = {1095-9203}, journal = {Science}, keywords = {multidisciplinary}, number = {6504}, publisher = {American Association for the Advancement of Science}, title = {{The proteasome controls ESCRT-III–mediated cell division in an archaeon}}, doi = {10.1126/science.aaz2532}, volume = {369}, year = {2020}, } @article{10350, abstract = {The misfolding and aberrant aggregation of proteins into fibrillar structures is a key factor in some of the most prevalent human diseases, including diabetes and dementia. Low molecular weight oligomers are thought to be a central factor in the pathology of these diseases, as well as critical intermediates in the fibril formation process, and as such have received much recent attention. Moreover, on-pathway oligomeric intermediates are potential targets for therapeutic strategies aimed at interrupting the fibril formation process. However, a consistent framework for distinguishing on-pathway from off-pathway oligomers has hitherto been lacking and, in particular, no consensus definition of on- and off-pathway oligomers is available. In this paper, we argue that a non-binary definition of oligomers' contribution to fibril-forming pathways may be more informative and we suggest a quantitative framework, in which each oligomeric species is assigned a value between 0 and 1 describing its relative contribution to the formation of fibrils. First, we clarify the distinction between oligomers and fibrils, and then we use the formalism of reaction networks to develop a general definition for on-pathway oligomers, that yields meaningful classifications in the context of amyloid formation. By applying these concepts to Monte Carlo simulations of a minimal aggregating system, and by revisiting several previous studies of amyloid oligomers in light of our new framework, we demonstrate how to perform these classifications in practice. For each oligomeric species we obtain the degree to which it is on-pathway, highlighting the most effective pharmaceutical targets for the inhibition of amyloid fibril formation.}, author = {Dear, Alexander J. and Meisl, Georg and Šarić, Anđela and Michaels, Thomas C. T. and Kjaergaard, Magnus and Linse, Sara and Knowles, Tuomas P. J.}, issn = {2041-6539}, journal = {Chemical Science}, keywords = {general chemistry}, number = {24}, pages = {6236--6247}, publisher = {Royal Society of Chemistry}, title = {{Identification of on- and off-pathway oligomers in amyloid fibril formation}}, doi = {10.1039/c9sc06501f}, volume = {11}, year = {2020}, } @article{10351, abstract = {Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.}, author = {Michaels, Thomas C. T. and Šarić, Anđela and Curk, Samo and Bernfur, Katja and Arosio, Paolo and Meisl, Georg and Dear, Alexander J. and Cohen, Samuel I. A. and Dobson, Christopher M. and Vendruscolo, Michele and Linse, Sara and Knowles, Tuomas P. J.}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {general chemical engineering, general chemistry}, number = {5}, pages = {445--451}, publisher = {Springer Nature}, title = {{Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide}}, doi = {10.1038/s41557-020-0452-1}, volume = {12}, year = {2020}, } @article{10352, abstract = {In the nuclear pore complex, intrinsically disordered nuclear pore proteins (FG Nups) form a selective barrier for transport into and out of the cell nucleus, in a way that remains poorly understood. The collective FG Nup behavior has long been conceptualized either as a polymer brush, dominated by entropic and excluded-volume (repulsive) interactions, or as a hydrogel, dominated by cohesive (attractive) interactions between FG Nups. Here we compare mesoscale computational simulations with a wide range of experimental data to demonstrate that FG Nups are at the crossover point between these two regimes. Specifically, we find that repulsive and attractive interactions are balanced, resulting in morphologies and dynamics that are close to those of ideal polymer chains. We demonstrate that this property of FG Nups yields sufficient cohesion to seal the transport barrier, and yet maintains fast dynamics at the molecular scale, permitting the rapid polymer rearrangements needed for transport events.}, author = {Davis, Luke K. and Ford, Ian J. and Šarić, Anđela and Hoogenboom, Bart W.}, issn = {2470-0053}, journal = {Physical Review E}, number = {2}, publisher = {American Physical Society}, title = {{Intrinsically disordered nuclear pore proteins show ideal-polymer morphologies and dynamics}}, doi = {10.1103/physreve.101.022420}, volume = {101}, year = {2020}, } @article{10353, abstract = {Experiments have suggested that bacterial mechanosensitive channels separate into 2D clusters, the role of which is unclear. By developing a coarse-grained computer model we find that clustering promotes the channel closure, which is highly dependent on the channel concentration and membrane stress. This behaviour yields a tightly regulated gating system, whereby at high tensions channels gate individually, and at lower tensions the channels spontaneously aggregate and inactivate. We implement this positive feedback into the model for cell volume regulation, and find that the channel clustering protects the cell against excessive loss of cytoplasmic content.}, author = {Paraschiv, Alexandru and Hegde, Smitha and Ganti, Raman and Pilizota, Teuta and Šarić, Anđela}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {4}, publisher = {American Physical Society}, title = {{Dynamic clustering regulates activity of mechanosensitive membrane channels}}, doi = {10.1103/physrevlett.124.048102}, volume = {124}, year = {2020}, } @article{21083, abstract = {Helically folded aromatic oligoamide foldamers have a size and geometrical parameters very distinct from those of α‐helices and are not obvious candidates for α‐helix mimicry. Nevertheless, they offer multiple sites for attaching side chains. It was found that some arrays of side chains at the surface of an aromatic helix make it possible to mimic extended α‐helical surfaces. Synthetic methods were developed to produce quinoline monomers suitably functionalized for solid phase synthesis. A dodecamer was prepared. Its crystal structure validated the initial design and showed helix bundling involving the α‐helix‐like interface. These results open up new uses of aromatic helices to recognize protein surfaces and to program helix bundling in water.}, author = {Zwillinger, Márton and Reddy, Post Sai and Wicher, Barbara and Mandal, Pradeep K and Csékei, Márton and Fischer, Lucile and Kotschy, András and Huc, Ivan}, issn = {1521-3765}, journal = {Chemistry – A European Journal}, number = {72}, pages = {17366--17370}, publisher = {Wiley}, title = {{Aromatic foldamer helices as α‐helix extended surface mimetics}}, doi = {10.1002/chem.202004064}, volume = {26}, year = {2020}, } @article{21084, abstract = {Self-assembly is a powerful method to obtain large discrete functional molecular architectures. When using a single building block, self-assembly generally yields symmetrical objects in which all the subunits relate similarly to their neighbours. Here we report the discovery of a family of self-constructing cyclic macromolecules with stable folded conformations of low symmetry, which include some with a prime number (13, 17 and 23) of units, despite being formed from a single component. The formation of these objects amounts to the production of polymers with a perfectly uniform length. Design rules for the spontaneous emergence of such macromolecules include endowing monomers with a strong potential for non-covalent interactions that remain frustrated in competing entropically favoured yet conformationally restrained smaller cycles. The process can also be templated by a guest molecule that itself has an asymmetrical structure, which paves the way to molecular imprinting techniques at the level of single polymer chains.}, author = {Pappas, Charalampos G. and Mandal, Pradeep K and Liu, Bin and Kauffmann, Brice and Miao, Xiaoming and Komáromy, Dávid and Hoffmann, Waldemar and Manz, Christian and Chang, Rayoon and Liu, Kai and Pagel, Kevin and Huc, Ivan and Otto, Sijbren}, issn = {1755-4349}, journal = {Nature Chemistry}, number = {12}, pages = {1180--1186}, publisher = {Springer Nature}, title = {{Emergence of low-symmetry foldamers from single monomers}}, doi = {10.1038/s41557-020-00565-2}, volume = {12}, year = {2020}, } @article{21085, abstract = {Foldamers combining aliphatic and aromatic main-chain units often produce atypical structures that cannot easily be accessed from purely aromatic or aliphatic sequences. We report solid-state evidence that sequences comprising α-amino acids and quinoline-based monomers adopt conformations that combine the folding propensities of both components. Foldamers 2 and 3 having an XQQ repeat motif (X=α-amino acid, Q=quinoline) were synthesized. Crystals of 2 (X=Phe, Q with an anionic side chain) obtained from water revealed an aromatic helix where amide groups belonging to the α-amino acids created a hydrogen-bond array typical of peptidic helices. Crystals of 3 (X=Ser, Q with a lipophilic side chain) obtained from organic solvents revealed a helix-turn-helix structure in which α-amino acid side chains interfere with main-chain hydrogen bonding. High sequence-dependency of the conformation is typical of peptides but is shown here to include aromatic folding features.}, author = {Hu, Xiaobo and Mandal, Pradeep K and Kauffmann, Brice and Huc, Ivan}, issn = {2192-6506}, journal = {ChemPlusChem}, number = {7}, pages = {1580--1586}, publisher = {Wiley}, title = {{Hybrid sequences that express both aromatic amide and α‐peptidic folding features}}, doi = {10.1002/cplu.202000416}, volume = {85}, year = {2020}, } @misc{17444, abstract = {The first wafer-scale growth of site-controlled Ge/Si nanowires is reported by Georgios Katsaros, Jian-Jun Zhang, and co-workers in article number 1906523. They are highly uniform and their position, distance, length, and even square- or L-shaped structures can all be precisely controlled. The electrically tunable spin-orbit coupling demonstrated by transport measurements and the charge sensing between quantum dots in closely spaced wires open a path toward scalable qubit devices using nanowires on silicon.}, author = {Gao, Fei and Wang, Jian‐Huan and Watzinger, Hannes and Hu, Hao and Rančić, Marko J. and Zhang, Jie‐Yin and Wang, Ting and Yao, Yuan and Wang, Gui‐Lei and Kukucka, Josip and Vukušić, Lada and Kloeffel, Christoph and Loss, Daniel and Liu, Feng and Katsaros, Georgios and Zhang, Jian‐Jun}, booktitle = {Advanced Materials}, issn = {1521-4095}, number = {16}, publisher = {Wiley}, title = {{Nanowires: Site‐controlled uniform Ge/Si Hut wires with electrically tunable spin–orbit coupling (Adv. Mater. 16/2020)}}, doi = {10.1002/adma.202070122}, volume = {32}, year = {2020}, } @article{17524, abstract = {The variability of quasars across multiple wavelengths is a useful probe of physical conditions in active galactic nuclei. In particular, variable accretion rates, instabilities, and reverberation effects in the accretion disc of a supermassive black hole are expected to produce correlated flux variations in ultraviolet (UV) and optical bands. Recent work has further argued that binary quasars should exhibit strongly correlated UV and optical periodicities. Strong UV–optical correlations have indeed been established in small samples of (N ≲ 30) quasars with well-sampled light curves, and have extended the ‘bluer-when-brighter’ trend previously found within the optical bands. Here, we further test the nature of quasar variability by examining the observed-frame UV–optical correlations among bright quasars extracted from the Half Million Quasars (HMQ) catalogue. We identified a large sample of 1315 quasars in HMQ with overlapping UV and optical light curves from the Galaxy Evolution Explorer and the Catalina Real-time Transient Survey, respectively. We find that strong correlations exist in this much larger sample, but we rule out, at ∼95 per cent confidence, the simple hypothesis that the intrinsic UV and optical variations of all quasars are fully correlated. Our results therefore imply the existence of physical mechanism(s) that can generate uncorrelated optical and UV flux variations.}, author = {Xin, Chengcheng and Charisi, Maria and Haiman, Zoltán and Schiminovich, David}, issn = {0035-8711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {1}, pages = {1403--1413}, publisher = {Oxford University Press}, title = {{Correlation between optical and UV variability of a large sample of quasars}}, doi = {10.1093/mnras/staa1258}, volume = {495}, year = {2020}, } @article{17528, abstract = {We performed a series of numerical experiments to quantify the sensitivity of the predictions for weak lensing statistics obtained in ray-tracing dark matter (DM)-only simulations, to two hyper-parameters that influence the accuracy as well as the computational cost of the predictions: the thickness of the lens planes used to build past light cones and the mass resolution of the underlying DM simulation. The statistics considered are the power spectrum (PS) and a series of non-Gaussian observables, including the one-point probability density function, lensing peaks, and Minkowski functionals. Counterintuitively, we find that using thin lens planes (< 60 h−1 Mpc on a 240 h−1 Mpc simulation box) suppresses the PS over a broad range of scales beyond what would be acceptable for a survey comparable to the Large Synoptic Survey Telescope (LSST). A mass resolution of 7.2 × 1011 h−1 M⊙ per DM particle (or 2563 particles in a (240 h−1 Mpc)3 box) is sufficient to extract information using the PS and non-Gaussian statistics from weak lensing data at angular scales down to 1' with LSST-like levels of shape noise.}, author = {Matilla, José Manuel Zorrilla and Waterval, Stefan and Haiman, Zoltán}, issn = {0004-6256}, journal = {The Astronomical Journal}, number = {6}, publisher = {American Astronomical Society}, title = {{Optimizing simulation parameters for weak lensing analyses involving non-Gaussian observables}}, doi = {10.3847/1538-3881/ab8f8c}, volume = {159}, year = {2020}, } @article{17529, abstract = {The astrophysical origin of gravitational wave (GW) events is one of the most timely problems in the wake of the LIGO/Virgo discoveries. In active galactic nuclei (AGN), binaries form and evolve efficiently by dynamical interactions and gaseous dissipation. Previous studies have suggested that binary black hole (BBH) mergers in AGN disks can contribute significantly to BBH mergers observed by GW interferometers. Here we examine the distribution of the effective spin parameter χeff of this GW source population. We extend our semi-analytical model of binary formation and evolution in AGN disks by following the evolution of the binary orbital angular momenta and black hole (BH) spins. BH spins change due to gas accretion and BH mergers, while the binary orbital angular momenta evolve due to gas accretion and binary-single interactions. We find that the distribution of χeff predicted by our AGN model is similar to the distribution observed during LIGO/Virgo O1 and O2. On the other hand, if radial migration of BHs is inefficient, χeff is skewed toward higher values compared with the observed distribution, because of the paucity of scattering events that would randomize spin directions relative to the orbital plane. We suggest that high binary masses and the positive correlation between binary mass and the standard deviation of χeff for chirp masses up to ≈20 M⊙, can be possible signatures for mergers originating in AGN disks. Finally, hierarchical mergers in AGN disks naturally produce properties of the recent GW event GW190412, including a low mass ratio, a high primary BH spin, and a significant spin component in the orbital plane.}, author = {Tagawa, Hiromichi and Haiman, Zoltán and Bartos, Imre and Kocsis, Bence}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {1}, publisher = {American Astronomical Society}, title = {{Spin evolution of stellar-mass black hole binaries in active galactic nuclei}}, doi = {10.3847/1538-4357/aba2cc}, volume = {899}, year = {2020}, } @article{17537, abstract = {The recent gravitational wave merger event, GW190521, has challenged our understanding of the stellar-mass black hole (BH) formation. The primary and secondary BH are both inferred to fall inside the pair-instability (PI) mass gap. Here we propose that the formation of such binaries is possible through gas accretion onto the BH remnants of Population III (Pop~III) stars born in high-redshift (z>10) minihalos. Once the parent halo has grown to the atomic-cooling limit, even brief episodes of gas accretion in the dense central regions of the halo can increase the masses of Pop~III remnant BHs above the PI limit. Starting with a BBH with an initial mass of O(100) M⊙ we find that it would only need to spend about 100~Myr in the inner few pc of an atomic-cooling halo to accrete about 50~M⊙ of material and resemble a system similar to GW190521. The dynamical friction timescale for the binary to sink to the dense inner region of its parent halo is comparable or shorter than the accretion timescale required to increase their mass above the PI limit. Once in the core of the halo, the binary can enter a phase of hyper-Eddington accretion, where it would only take a few thousand years to exceed the PI limit through accretion. Even more massive BBHs could form through this channel, and be detectable by detectors with improved low-frequency sensitivity. Single Pop~III BH remnants would also grow through accretion and could later form binaries dynamically. As little as a few percent of Pop~III BH remnants may be sufficient to match the rate of massive BBH mergers inferred from GW190521 of 0.13+0.3−0.11Gpc−3yr−1.}, author = {Safarzadeh, Mohammadtaher and Haiman, Zoltán}, issn = {2041-8205}, journal = {The Astrophysical Journal Letters}, number = {1}, publisher = {American Astronomical Society}, title = {{Formation of GW190521 via gas accretion onto population III stellar black hole remnants born in high-redshift minihalos}}, doi = {10.3847/2041-8213/abc253}, volume = {903}, year = {2020}, }