@inproceedings{9987, abstract = {Stateless model checking (SMC) is one of the standard approaches to the verification of concurrent programs. As scheduling non-determinism creates exponentially large spaces of thread interleavings, SMC attempts to partition this space into equivalence classes and explore only a few representatives from each class. The efficiency of this approach depends on two factors: (a) the coarseness of the partitioning, and (b) the time to generate representatives in each class. For this reason, the search for coarse partitionings that are efficiently explorable is an active research challenge. In this work we present RVF-SMC , a new SMC algorithm that uses a novel reads-value-from (RVF) partitioning. Intuitively, two interleavings are deemed equivalent if they agree on the value obtained in each read event, and read events induce consistent causal orderings between them. The RVF partitioning is provably coarser than recent approaches based on Mazurkiewicz and “reads-from” partitionings. Our experimental evaluation reveals that RVF is quite often a very effective equivalence, as the underlying partitioning is exponentially coarser than other approaches. Moreover, RVF-SMC generates representatives very efficiently, as the reduction in the partitioning is often met with significant speed-ups in the model checking task.}, author = {Agarwal, Pratyush and Chatterjee, Krishnendu and Pathak, Shreya and Pavlogiannis, Andreas and Toman, Viktor}, booktitle = {33rd International Conference on Computer-Aided Verification }, isbn = {978-3-030-81684-1}, issn = {1611-3349}, location = {Virtual}, pages = {341--366}, publisher = {Springer Nature}, title = {{Stateless model checking under a reads-value-from equivalence}}, doi = {10.1007/978-3-030-81685-8_16}, volume = {12759 }, year = {2021}, } @phdthesis{9992, abstract = {Blood – this is what animals use to heal wounds fast and efficient. Plants do not have blood circulation and their cells cannot move. However, plants have evolved remarkable capacities to regenerate tissues and organs preventing further damage. In my PhD research, I studied the wound healing in the Arabidopsis root. I used a UV laser to ablate single cells in the root tip and observed the consequent wound healing. Interestingly, the inner adjacent cells induced a division plane switch and subsequently adopted the cell type of the killed cell to replace it. We termed this form of wound healing “restorative divisions”. This initial observation triggered the questions of my PhD studies: How and why do cells orient their division planes, how do they feel the wound and why does this happen only in inner adjacent cells. For answering these questions, I used a quite simple experimental setup: 5 day - old seedlings were stained with propidium iodide to visualize cell walls and dead cells; ablation was carried out using a special laser cutter and a confocal microscope. Adaptation of the novel vertical microscope system made it possible to observe wounds in real time. This revealed that restorative divisions occur at increased frequency compared to normal divisions. Additionally, the major plant hormone auxin accumulates in wound adjacent cells and drives the expression of the wound-stress responsive transcription factor ERF115. Using this as a marker gene for wound responses, we found that an important part of wound signalling is the sensing of the collapse of the ablated cell. The collapse causes a radical pressure drop, which results in strong tissue deformations. These deformations manifest in an invasion of the now free spot specifically by the inner adjacent cells within seconds, probably because of higher pressure of the inner tissues. Long-term imaging revealed that those deformed cells continuously expand towards the wound hole and that this is crucial for the restorative division. These wound-expanding cells exhibit an abnormal, biphasic polarity of microtubule arrays before the division. Experiments inhibiting cell expansion suggest that it is the biphasic stretching that induces those MT arrays. Adapting the micromanipulator aspiration system from animal scientists at our institute confirmed the hypothesis that stretching influences microtubule stability. In conclusion, this shows that microtubules react to tissue deformation and this facilitates the observed division plane switch. This puts mechanical cues and tensions at the most prominent position for explaining the growth and wound healing properties of plants. Hence, it shines light onto the importance of understanding mechanical signal transduction. }, author = {Hörmayer, Lukas}, issn = {2663-337X}, pages = {168}, publisher = {Institute of Science and Technology Austria}, title = {{Wound healing in the Arabidopsis root meristem}}, doi = {10.15479/at:ista:9992}, year = {2021}, } @article{9997, abstract = {Indirect reciprocity is a mechanism for the evolution of cooperation based on social norms. This mechanism requires that individuals in a population observe and judge each other’s behaviors. Individuals with a good reputation are more likely to receive help from others. Previous work suggests that indirect reciprocity is only effective when all relevant information is reliable and publicly available. Otherwise, individuals may disagree on how to assess others, even if they all apply the same social norm. Such disagreements can lead to a breakdown of cooperation. Here we explore whether the predominantly studied ‘leading eight’ social norms of indirect reciprocity can be made more robust by equipping them with an element of generosity. To this end, we distinguish between two kinds of generosity. According to assessment generosity, individuals occasionally assign a good reputation to group members who would usually be regarded as bad. According to action generosity, individuals occasionally cooperate with group members with whom they would usually defect. Using individual-based simulations, we show that the two kinds of generosity have a very different effect on the resulting reputation dynamics. Assessment generosity tends to add to the overall noise and allows defectors to invade. In contrast, a limited amount of action generosity can be beneficial in a few cases. However, even when action generosity is beneficial, the respective simulations do not result in full cooperation. Our results suggest that while generosity can favor cooperation when individuals use the most simple strategies of reciprocity, it is disadvantageous when individuals use more complex social norms.}, author = {Schmid, Laura and Shati, Pouya and Hilbe, Christian and Chatterjee, Krishnendu}, issn = {2045-2322}, journal = {Scientific Reports}, keywords = {Multidisciplinary}, number = {1}, publisher = {Springer Nature}, title = {{The evolution of indirect reciprocity under action and assessment generosity}}, doi = {10.1038/s41598-021-96932-1}, volume = {11}, year = {2021}, } @article{9998, abstract = {We define quantum equivariant K-theory of Nakajima quiver varieties. We discuss type A in detail as well as its connections with quantum XXZ spin chains and trigonometric Ruijsenaars-Schneider models. Finally we study a limit which produces a K-theoretic version of results of Givental and Kim, connecting quantum geometry of flag varieties and Toda lattice.}, author = {Koroteev, Peter and Pushkar, Petr and Smirnov, Andrey V. and Zeitlin, Anton M.}, issn = {1420-9020}, journal = {Selecta Mathematica}, number = {5}, publisher = {Springer Nature}, title = {{Quantum K-theory of quiver varieties and many-body systems}}, doi = {10.1007/s00029-021-00698-3}, volume = {27}, year = {2021}, } @article{9999, abstract = {The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors’ movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development. Impact Statement: Incomplete delamination serves as a cellular platform for coordinated tissue movements during development, guiding newly formed progenitor cell groups to the differentiation site.}, author = {Pulgar, Eduardo and Schwayer, Cornelia and Guerrero, Néstor and López, Loreto and Márquez, Susana and Härtel, Steffen and Soto, Rodrigo and Heisenberg, Carl Philipp and Concha, Miguel L.}, issn = {2050-084X}, journal = {eLife}, keywords = {cell delamination, apical constriction, dragging, mechanical forces, collective 18 locomotion, dorsal forerunner cells, zebrafish}, publisher = {eLife Sciences Publications}, title = {{Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism}}, doi = {10.7554/eLife.66483}, volume = {10}, year = {2021}, } @unpublished{10012, abstract = {We prove that in the absence of topological changes, the notion of BV solutions to planar multiphase mean curvature flow does not allow for a mechanism for (unphysical) non-uniqueness. Our approach is based on the local structure of the energy landscape near a classical evolution by mean curvature. Mean curvature flow being the gradient flow of the surface energy functional, we develop a gradient-flow analogue of the notion of calibrations. Just like the existence of a calibration guarantees that one has reached a global minimum in the energy landscape, the existence of a "gradient flow calibration" ensures that the route of steepest descent in the energy landscape is unique and stable.}, author = {Fischer, Julian L and Hensel, Sebastian and Laux, Tim and Simon, Thilo}, booktitle = {arXiv}, title = {{The local structure of the energy landscape in multiphase mean curvature flow: weak-strong uniqueness and stability of evolutions}}, year = {2020}, } @unpublished{10022, abstract = {We consider finite-volume approximations of Fokker-Planck equations on bounded convex domains in R^d and study the corresponding gradient flow structures. We reprove the convergence of the discrete to continuous Fokker-Planck equation via the method of Evolutionary Γ-convergence, i.e., we pass to the limit at the level of the gradient flow structures, generalising the one-dimensional result obtained by Disser and Liero. The proof is of variational nature and relies on a Mosco convergence result for functionals in the discrete-to-continuum limit that is of independent interest. Our results apply to arbitrary regular meshes, even though the associated discrete transport distances may fail to converge to the Wasserstein distance in this generality.}, author = {Forkert, Dominik L and Maas, Jan and Portinale, Lorenzo}, booktitle = {arXiv}, pages = {33}, title = {{Evolutionary Γ-convergence of entropic gradient flow structures for Fokker-Planck equations in multiple dimensions}}, year = {2020}, } @inproceedings{10328, abstract = {We discus noise channels in coherent electro-optic up-conversion between microwave and optical fields, in particular due to optical heating. We also report on a novel configuration, which promises to be flexible and highly efficient.}, author = {Lambert, Nicholas J. and Mobassem, Sonia and Rueda Sanchez, Alfredo R and Schwefel, Harald G.L.}, booktitle = {OSA Quantum 2.0 Conference}, isbn = {9-781-5575-2820-9}, location = {Washington, DC, United States}, publisher = {Optica Publishing Group}, title = {{New designs and noise channels in electro-optic microwave to optical up-conversion}}, doi = {10.1364/QUANTUM.2020.QTu8A.1}, year = {2020}, } @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}, }