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| Open AccessIn-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells
I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single stranded, cytosine-rich genomic region, but the specific contributions of several factors involved in their formation are unknown. Using in-cell NMR, the authors examined DNA i-motif formation in human cells at body temperature, suggesting i-M occur in a small portion (<1%) of genomic sites predisposed to its formation.
- Pavlína Víšková
- , Eva Ištvánková
- & Lukáš Trantírek
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Article
| Open AccessHeterotypic interactions can drive selective co-condensation of prion-like low-complexity domains of FET proteins and mammalian SWI/SNF complex
Prion-like domains are intrinsically disordered regions found in many RNA- and DNA-binding proteins. Here, the authors show that these domains can drive sequence-specific co-phase separation of chromatin remodeling complex with FET oncofusion proteins.
- Richoo B. Davis
- , Anushka Supakar
- & Priya R. Banerjee
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Article
| Open AccessHydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis
It is vital to unveil the effects of extracellular matrix cues on endothelial cell (EC) outgrowth for desirably governing vasculature formation, but the role of matrix plasticity on EC outgrowth is elusive. Here, the authors develop hydrogels with tunable mechanical plasticity independent of stiffness, and elucidate the plasticity-mediated responses of ECs during vasculogenesis and angiogenesis.
- Zhao Wei
- , Meng Lei
- & Feng Xu
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| Open AccessTargeting nucleic acid phase transitions as a mechanism of action for antimicrobial peptides
In this work the authors describe antimicrobial peptides (AMPs)-driven phase transitions of intracellular nucleic acids, whereby AMPs induce compaction and phase separation of nucleic acids, resulting in their sequestration and eventual cell death.
- Tomas Sneideris
- , Nadia A. Erkamp
- & Tuomas P. J. Knowles
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Article
| Open AccessBiophysical ordering transitions underlie genome 3D re-organization during cricket spermiogenesis
Orsi et al. identify an elegant solution to DNA packing in cricket sperm nuclei, whereby relatively simple biophysical changes in chromatin properties result in a liquid crystal-like twisted spool organization that favors ultracompaction.
- Guillermo A. Orsi
- , Maxime M. C. Tortora
- & Benjamin Loppin
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Article
| Open AccessBacterial capsular polysaccharides with antibiofilm activity share common biophysical and electrokinetic properties
Bacteria produce several high molecular weight polysaccharides with ill-defined anti-adhesion properties. Here, the authors identified key molecular and biophysical determinants of active antibiofilm polysaccharides, opening new perspectives to identify or engineer new compounds able to control bacterial adhesion and biofilm formation.
- Joaquín Bernal-Bayard
- , Jérôme Thiebaud
- & Jean-Marc Ghigo
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Article
| Open AccessRNA-mediated demixing transition of low-density condensates
The cell interior is organized by diverse membrane-less condensates. Here, the authors reveal that the densities of certain condensates are surprisingly low, similar to the surrounding protoplasm and driven by cellular RNA as well as the crowded milieu.
- Taehyun Kim
- , Jaeyoon Yoo
- & Yongdae Shin
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Article
| Open AccessThe F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation
Enteropathogenic bacteria use extracellular appendages, known as F-pili, to share plasmids carrying antibiotic resistance genes. Here, the authors show that F-pili are highly flexible but robust at the same time, and this is important for plasmid transfer and formation of biofilms that protect against the action of antibiotics.
- Jonasz B. Patkowski
- , Tobias Dahlberg
- & Tiago R. D. Costa
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Article
| Open AccessThe ϕPA3 phage nucleus is enclosed by a self-assembling 2D crystalline lattice
To protect from host attack, numerous jumbo bacteriophages establish a micron-scale, protein-based structure to enclose their replicating DNA. Using cryoEM, the authors show that the 2D crystal enclosing this so-called phage nucleus is an assembly of tetramers linked by flexible loops and tails.
- Eliza S. Nieweglowska
- , Axel F. Brilot
- & David A. Agard
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Article
| Open AccessNative structure of mosquito salivary protein uncovers domains relevant to pathogen transmission
Female mosquitoes inject saliva into vertebrate hosts during blood feeding, transmitting mosquito-borne pathogens. Here, cryo-EM of mosquito salivary gland extract uncovers the native SGS1 structure and domains relevant to pathogen transmission.
- Shiheng Liu
- , Xian Xia
- & Z. Hong Zhou
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Article
| Open AccessPolymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models
Nanotherapy has potential utility in cancer, particularly in targeted delivery of therapeutics. Here the authors demonstrate delivery of tranilast loaded micelles to improve the reprogramming of cancer associated fibroblasts and monitor tumour stiffness to predict responses.
- Myrofora Panagi
- , Fotios Mpekris
- & Triantafyllos Stylianopoulos
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Article
| Open AccessA simple thermodynamic description of phase separation of Nup98 FG domains
The nuclear pore complex (NPC) barrier is a selective phase assembled from disordered but cohesive FG domains. The authors provide a thermodynamic description of an FG phase that is ultimately simplified and yet closely recapitulates NPC transport selectivity.
- Sheung Chun Ng
- & Dirk Görlich
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Article
| Open AccessThe architecture and operating mechanism of a cnidarian stinging organelle
The venomous stinging cells of jellyfish, anemones, and corals contain an organelle, the nematocyst, which explosively discharges a venom-laden thread. Here, the authors describe the nematocyst thread and its sub-structures in the sea anemone N. vectensis, revealing a complexity and sophistication underpinning this cellular weapon.
- Ahmet Karabulut
- , Melainia McClain
- & Matthew C. Gibson
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Article
| Open AccessDynamic stiffening of the flagellar hook
Bacterial motility relies on the mechanics of the “hook” the 60 nm biopolymer at the base of rotating flagella. Here, authors observe the hook stiffening as it is twisted by the rotation of the flagellum, a mechanical feat evolved for its function.
- Ashley L. Nord
- , Anaïs Biquet-Bisquert
- & Francesco Pedaci
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Article
| Open AccessExtensible and self-recoverable proteinaceous materials derived from scallop byssal thread
Bio-inspired materials are an intense area of study as researchers try to adapt biomaterials for other applications. Here, the authors report on the processing of protein materials derived from the byssal thread of scallops to create high-extensibility materials with self-recovery under wet conditions.
- Xiaokang Zhang
- , Mengkui Cui
- & Weizhi Liu
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Article
| Open AccessFilopodia rotate and coil by actively generating twist in their actin shaft
The authors show how tubular surface structures in all cell types, have the ability to twist and perform rotary sweeping motion to explore the extracellular environment. This has implications for migration, sensing and cell communication.
- Natascha Leijnse
- , Younes Farhangi Barooji
- & Poul Martin Bendix
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| Open AccessAtomic resolution dynamics of cohesive interactions in phase-separated Nup98 FG domains
The permeability barrier of nuclear pores is formed by disordered and yet self-interacting FG repeat domains, whose sequence heterogeneity is a challenge for mechanistic insights. Here the authors overcome this challenge and characterize the protein’s dynamics by applying NMR techniques to an FG phase system that has been simplified to its essentials.
- Eszter E. Najbauer
- , Sheung Chun Ng
- & Loren B. Andreas
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| Open AccessA general theoretical framework to design base editors with reduced bystander effects
Base editors can edit target nucleotides, and identical ones that are within the editing window. Here the authors build an analytical model to propose general principles of editor design to reduce bystander effects.
- Qian Wang
- , Jie Yang
- & Anatoly B. Kolomeisky
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Article
| Open AccessShear relaxation governs fusion dynamics of biomolecular condensates
Phase-separated biomolecular condensates are implicated in a myriad of biological processes. Here the authors apply optical tweezers to characterize the viscoelasticity and interfacial tension of a range of condensates, finding that condensates can deviate from simple fluids in opposite directions; and identify shear relaxation as a governing measure of condensate dynamics.
- Archishman Ghosh
- , Divya Kota
- & Huan-Xiang Zhou
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| Open AccessIntrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells
Methods to monitor osmolarity-dependent changes in cell are currently lacking. Here the authors use the Arabidopsis intrinsically disordered AtLEA4-5 protein, which is expressed in plants under water deficit, to develop a FRET biosensor (SED1) to monitor osmotic stress.
- Cesar L. Cuevas-Velazquez
- , Tamara Vellosillo
- & José R. Dinneny
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| Open AccessNonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina
Mechanical strength of in situ assembled nuclear lamin filaments arranged in a 3D meshwork is unclear. Here, using mechanical, structural and simulation tools, the authors report the hierarchical organization of the lamin meshwork that imparts strength and toughness to lamin filaments at par with silk and Kevlar®
- K. Tanuj Sapra
- , Zhao Qin
- & Ohad Medalia
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Article
| Open AccessSynthesis runs counter to directional folding of a nascent protein domain
In vivo experiments and optical tweezers force-spectroscopy measurements assessing the co-translational folding of the G-domain from bacterial elongation factor G reveal a sequential folding pathway initiating from the C-terminus. These results suggest that protein folding and synthesis proceed in opposite directions.
- Xiuqi Chen
- , Nandakumar Rajasekaran
- & Christian M. Kaiser
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Article
| Open AccessTunable multiphase dynamics of arginine and lysine liquid condensates
The design principles underlying biomolecular phase separation of membrane-less organelles remain poorly understood. Using model homopolymers, Fisher et al. show that the formation kinetics of coexisting liquid phases can be tuned by exploiting differences between arginine and lysine residues.
- Rachel S. Fisher
- & Shana Elbaum-Garfinkle
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Article
| Open AccessMechanoradicals in tensed tendon collagen as a source of oxidative stress
The existence, nature and biological relevance of mechanoradicals in proteins are unknown. Here authors show that mechanical stress on collagen produces radicals and subsequently reactive oxygen species and suggest that collagen I evolved as a radical sponge against mechano-oxidative damage.
- Christopher Zapp
- , Agnieszka Obarska-Kosinska
- & Frauke Gräter
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Article
| Open AccessRigidity enhances a magic-number effect in polymer phase separation
The phase separation of two species of associating polymers is suppressed by a magic-number effect for certain combinations of the numbers of binding sites. Here the authors use lattice simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one component has a rigid shape.
- Bin Xu
- , Guanhua He
- & Ned S. Wingreen
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Article
| Open AccessChiral twisting in a bacterial cytoskeletal polymer affects filament size and orientation
The actin homolog MreB directs cell-wall insertion and maintains cell shape in many rod-shaped bacteria. Here, Shi et al. perform molecular dynamics simulations for MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that predicts MreB filament properties.
- Handuo Shi
- , David A. Quint
- & Kerwyn Casey Huang
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Article
| Open AccessLive cell imaging of single RNA molecules with fluorogenic Mango II arrays
Fluorogenic RNA aptamers have been used for RNA imaging, but folding and fluorescence stability often limited their use in high resolution applications. Here the authors present an array of stably folding Mango II aptamers for imaging of coding and non-coding RNAs at single-molecule resolution, in both live and fixed cells.
- Adam D. Cawte
- , Peter J. Unrau
- & David S. Rueda
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Article
| Open AccessHierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases
The mussel byssus cuticle is a wear-resistant and extensible metalloprotein composite. Here, the authors probed the cuticle nanostructure and composition before, during and after fabrication revealing a crucial role of metal-binding proteins that self-organize via liquid-liquid phase separation.
- Franziska Jehle
- , Elena Macías-Sánchez
- & Matthew J. Harrington
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| Open AccessActive topological glass
Glass transition in soft materials can be affected by the topology of constituent particles, but the detail remains elusive. Here, Smrek et al. show that the interplay between circular topology of ring polymers and their active segments generates a new state of matter, namely active topological glass.
- Jan Smrek
- , Iurii Chubak
- & Kurt Kremer
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Article
| Open AccessRNA is a critical element for the sizing and the composition of phase-separated RNA–protein condensates
RNA promotes liquid-liquid phase separation and contributes to the ribonucleoprotein granule assembly. Here the authors employ the protein scaffold ArtiGranule and show the role of intracellular RNA in nucleation and sizing of the phase separated condensates.
- Marina Garcia-Jove Navarro
- , Shunnichi Kashida
- & Zoher Gueroui
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Article
| Open AccessDesign and fabrication of flexible DNA polymer cocoons to encapsulate live cells
The ability to encapsulate living cells could lead to many applications. Here, the authors present a flexible method to graft DNA polymers onto bacteria, yeast and mammalian cells, polymerize them into DNA cocoons and use these to manipulate and select cells based on the encoded polymer sequences on DNA cocoons.
- Tao Gao
- , Tianshu Chen
- & Genxi Li
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Article
| Open AccessChromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions
Antibodies are generated through remote genomic interactions involving immunoglobulin variable (VH), diversity (DH) and joining (JH) gene segments. Here the authors develop a strategy to track VH-DHJH motion in B-lymphocytes and provide evidence that chromosome organisation near the sol-gel phase transition dictates the timing of genomic interactions to orchestrate gene expression and somatic recombination.
- Nimish Khanna
- , Yaojun Zhang
- & Cornelis Murre
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Article
| Open AccessTopologically-guided continuous protein crystallization controls bacterial surface layer self-assembly
Bacteria assemble the surface layer (S-layer), a crystalline protein coat surrounding the curved surface, using protein self-assembly. Here authors image native and purified RsaA, the S-layer protein from C. crescentus, and show that protein crystallization alone is sufficient to assemble and maintain the S-layer in vivo.
- Colin J. Comerci
- , Jonathan Herrmann
- & W. E. Moerner
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Article
| Open AccessCentromere mechanical maturation during mammalian cell mitosis
During mitosis, tension at the centromere occurs from the spindle but the role of centromere mechanics in controlling metaphase tension is poorly understood. Here, the authors report that mechanical stiffnness of the centromere matures during mitotic progression and is amplified specifically at metaphase.
- Lauren A. Harasymiw
- , Damien Tank
- & Melissa K. Gardner
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Article
| Open AccessInfluenza A virus ribonucleoproteins form liquid organelles at endoplasmic reticulum exit sites
Influenza A virus forms cytosolic inclusions containing viral ribonucleoproteins. Here, the authors show that viral inclusions form juxtaposed the endoplasmic reticulum and have liquid properties, likely constituting sites of assembly of epidemic and pandemic influenza genomes.
- Marta Alenquer
- , Sílvia Vale-Costa
- & Maria João Amorim
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Article
| Open AccessQuantifying protein dynamics and stability in a living organism
Studying protein kinetics and stability in living organisms is challenging and most studies are performed in cell culture. Here the authors combine meganuclease-mediated transformation and fluorescence-detected temperature-jump microscopy to quantify protein stability in different tissues of living zebrafish.
- Ruopei Feng
- , Martin Gruebele
- & Caitlin M. Davis
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Article
| Open AccessMuc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice
The promoter variant rs35705950 confers a gain of function to the MUC5B gene and is the dominant risk factor for idiopathic pulmonary fibrosis. Here the authors show that mice overexpressing Muc5b in distal airspaces show impaired mucociliary clearance and increased susceptibility to bleomycin-induced lung fibrosis, and that both characteristics are reduced by treatment with a mucolytic agent.
- Laura A. Hancock
- , Corinne E. Hennessy
- & David A. Schwartz
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Article
| Open AccessCompositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms
The nucleolus is a membrane-less organelle and both Nucleophosmin (NPM1) and Surfeit locus protein 6 (SURF6) are abundant proteins within the nucleolus. Here the authors employ biophysical methods to study the properties of NPM1-S6N droplets and provide insights into the role of SURF6 in maintaining and modulating the liquid-like structure of the nucleolus.
- Mylene C. Ferrolino
- , Diana M. Mitrea
- & Richard W. Kriwacki
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Article
| Open AccessInteractions between callose and cellulose revealed through the analysis of biopolymer mixtures
Despite their importance in plant development and defence the properties of (1,3)-β-glucan remain largely unknown. Here, the authors find that addition of (1,3)-β-glucans increases the flexibility of cellulose and its resilience to high strain, an effect originating in molecular level interactions.
- Radwa H. Abou-Saleh
- , Mercedes C. Hernandez-Gomez
- & Yoselin Benitez-Alfonso
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Article
| Open AccessTheoretical principles of transcription factor traffic on folded chromatin
How transcription factors find their targets in vivo is still poorly understood. Here the authors use molecular dynamics simulations to investigate how transcription factors diffuse on chromatin, providing a theoretical framework for understanding the key role of genome conformation in this process.
- Ruggero Cortini
- & Guillaume J. Filion
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Article
| Open AccessOptogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres
Cellular contractility is regulated by the GTPase RhoA, but how local signals are translated to a cell-level response is not known. Here the authors show that targeted RhoA activation results in propagation of force along stress fibres and actin flow, and identify zyxin as a regulator of stress fibre mechanics and homeostasis.
- Patrick W. Oakes
- , Elizabeth Wagner
- & Margaret L. Gardel
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Article
| Open AccessSelf-organizing actin patterns shape membrane architecture but not cell mechanics
In vitro models of actin organization show the formation of vortices, asters and stars. Here Fritzsche et al. show that such actin structures form in living cells in a manner dependent on the Arp2/3 complex but not myosin, and such structures influence membrane architecture but not cortex elasticity.
- M. Fritzsche
- , D. Li
- & C. Eggeling
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Article
| Open AccessDisordered actomyosin networks are sufficient to produce cooperative and telescopic contractility
The interaction between myosin motors and F-actin is well described, but the impact of actin organization on contractility is not well described. Here the authors use a 2D biomimetic system and computational modelling to show that contractility of isotropic actomyosin is cooperative, and contraction velocity scales with myosin activation area.
- Ian Linsmeier
- , Shiladitya Banerjee
- & Michael P. Murrell
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Two-way traffic of glycoside hydrolase family 18 processive chitinases on crystalline chitin
The degradation of chitin and cellulose is dependent on the processivity of degrading enzymes. Here, Igarashi et al. use high-speed atomic force microscopy to visualize the movement of two chitinases (ChiA and ChiB) and show them to move in opposite directions, allowing a molecular mechanism to be proposed.
- Kiyohiko Igarashi
- , Takayuki Uchihashi
- & Masahiro Samejima
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Coiling and maturation of a high-performance fibre in hagfish slime gland thread cells
Hagfish slime contains fibres that are produced in gland cells, but how these threads are assembled within the cell is unclear. Here, using electron microscopy and three-dimensional modelling, the authors show that during gland cell maturation the shape of the nucleus changes, permitting the coiling of the threads around it.
- Timothy Winegard
- , Julia Herr
- & Douglas Fudge
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A synthetic icosahedral DNA-based host–cargo complex for functional in vivo imaging
Encapsulating molecules within supramolecular frameworks for potential biological application is challenging. Bhatiaet al. incorporate a fluorescent polymer within an icosahedral DNA nanocapsule, and show that it can be used to target specific cells in vivoand map pH spatially and temporally.
- Dhiraj Bhatia
- , Sunaina Surana
- & Yamuna Krishnan