@article{10867, abstract = {In this paper we find a tight estimate for Gromov’s waist of the balls in spaces of constant curvature, deduce the estimates for the balls in Riemannian manifolds with upper bounds on the curvature (CAT(ϰ)-spaces), and establish similar result for normed spaces.}, author = {Akopyan, Arseniy and Karasev, Roman}, issn = {1687-0247}, journal = {International Mathematics Research Notices}, keywords = {General Mathematics}, number = {3}, pages = {669--697}, publisher = {Oxford University Press}, title = {{Waist of balls in hyperbolic and spherical spaces}}, doi = {10.1093/imrn/rny037}, volume = {2020}, year = {2020}, } @article{11054, abstract = {In recent years, the nuclear pore complex (NPC) has emerged as a key player in genome regulation and cellular homeostasis. New discoveries have revealed that the NPC has multiple cellular functions besides mediating the molecular exchange between the nucleus and the cytoplasm. In this review, we discuss non-transport aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity of the NPC proteins, and NPC dysfunction in age-related diseases. The examples summarized herein demonstrate that the NPC, which first evolved to enable the biochemical communication between the nucleus and the cytoplasm, now doubles as the gatekeeper of cellular identity and aging.}, author = {Cho, Ukrae H. and HETZER, Martin W}, issn = {0896-6273}, journal = {Neuron}, keywords = {General Neuroscience}, number = {6}, pages = {899--911}, publisher = {Elsevier}, title = {{Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging}}, doi = {10.1016/j.neuron.2020.05.031}, volume = {106}, year = {2020}, } @article{11055, abstract = {Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.}, author = {Bersini, Simone and Schulte, Roberta and Huang, Ling and Tsai, Hannah and HETZER, Martin W}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications}, title = {{Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome}}, doi = {10.7554/elife.54383}, volume = {9}, year = {2020}, } @article{11056, abstract = {Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age-dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ-specific vascular endothelial cells (VECs). Long-living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA-seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin-like-4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established.}, author = {Bersini, Simone and Arrojo e Drigo, Rafael and Huang, Ling and Shokhirev, Maxim N. and HETZER, Martin W}, issn = {2366-7478}, journal = {Advanced Biosystems}, keywords = {General Biochemistry, Genetics and Molecular Biology, Biomedical Engineering, Biomaterials}, number = {5}, publisher = {Wiley}, title = {{Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease}}, doi = {10.1002/adbi.202000044}, volume = {4}, year = {2020}, } @article{11057, abstract = {During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/telophase is required for posttranscriptional activation and may play a role in the establishment of topologically associating domains (TADs). Together, our results suggest that the genome is reorganized in a sequential order, in which histone methylations occur first in prometaphase, histone acetylation, and CTCF in anaphase/telophase, transcription in cytokinesis, and long-range chromatin interactions in early G1. We thus provide insights into the histone modification landscape that allows faithful reestablishment of the transcriptional program and TADs during cell division.}, author = {Kang, Hyeseon and Shokhirev, Maxim N. and Xu, Zhichao and Chandran, Sahaana and Dixon, Jesse R. and HETZER, Martin W}, issn = {0890-9369}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {13-14}, pages = {913--930}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation}}, doi = {10.1101/gad.335794.119}, volume = {34}, year = {2020}, } @article{11058, abstract = {Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.}, author = {Bersini, Simone and Lytle, Nikki K and Schulte, Roberta and Huang, Ling and Wahl, Geoffrey M and HETZER, Martin W}, issn = {2575-1077}, journal = {Life Science Alliance}, keywords = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology}, number = {1}, publisher = {Life Science Alliance}, title = {{Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling}}, doi = {10.26508/lsa.201900623}, volume = {3}, 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}, } @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}, }