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| Open AccessVoltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state
It is believed that voltage sensor domains (VSD) of voltage-gated Na+ channels are always attached to the channel. Here, authors find that VSDs detach from the channel to form inter-channel dimers.
- Ayumi Sumino
- , Takashi Sumikama
- & Katsumasa Irie
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Article
| Open AccessA tradeoff between enterovirus A71 particle stability and cell entry
Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. Here, the authors show that a single mutation in enterovirus A71 capsid affects the balance between particle stability and cell entry efficiency. Structural and simulation analyses reveal an expanded conformation in the thermostable viruses, resulting in increased particle flexibility.
- Adam Catching
- , Ming Te Yeh
- & Raul Andino
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Article
| Open AccessVisualizing ultrafast photothermal dynamics with decoupled optical force nanoscopy
Diving deep into material insights, the authors introduce the ‘Decoupled Optical Force Nanoscopy’. This innovation uncovers the physical origins of light induced forces and captures dynamic thermal details with unparalleled nanometer precision.
- Hanwei Wang
- , Sean M. Meyer
- & Yang Zhao
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Article
| Open AccessA concerted ATPase cycle of the protein transporter AAA-ATPase Bcs1
Bcs1, a transmembrane AAA-ATPase, facilitates the translocation of folded ISP across the inner mitochondrial membrane. This study shows that the Bcs1 ATPase cycle conformational changes are highly concerted, unlike the canonical hand-over-hand mechanism.
- Yangang Pan
- , Jingyu Zhan
- & Simon Scheuring
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Article
| Open AccessVisualizing the membrane disruption action of antimicrobial peptides by cryo-electron tomography
Antimicrobial peptide mechanism of membrane disruption have not been fully characterized at the cellular level. Here, authors use cryo-electron tomography and AFM to directly visualize the disruption of the outer and inner membranes of Escherichia coli by a de novo-designed peptide.
- Eric H.-L. Chen
- , Chun-Hsiung Wang
- & Rita P.-Y. Chen
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Matters Arising
| Open AccessReply to: Antibiotics and hexagonal order in the bacterial outer membrane
- Selen Manioglu
- , Seyed Majed Modaresi
- & Sebastian Hiller
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Article
| Open AccessSingle-molecular insights into the breakpoint of cellulose nanofibers assembly during saccharification
Lignocellulose recalcitrance hampers its utilization for the production of biofuels and biosourced chemicals. Here, the authors reveal that the amorphous cellulose is the breakpoint of interact microfibrils and propose OsFC16/CESA9 as the engineering target to increase saccharification ability.
- Ran Zhang
- , Zhen Hu
- & Liangcai Peng
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Article
| Open AccessAmyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes
Bhardwaj et al., have explored the proteomes of SARS-CoV and SARS-CoV-2, and have demonstrated the amyloid formation of viral proteins, in vitro, through diverse biophysical techniques.
- Taniya Bhardwaj
- , Kundlik Gadhave
- & Rajanish Giri
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Article
| Open AccessVisualizing RNA conformational and architectural heterogeneity in solution
RNA conformational heterogeneity is important to diverse functions. Here, the authors use AFM to directly visualize individual RNA molecules that are in various conformational states under near physiological solution conditions for the first time.
- Jienyu Ding
- , Yun-Tzai Lee
- & Yun-Xing Wang
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Article
| Open AccessResolving the intrinsic short-range ordering of K+ ions on cleaved muscovite mica
Mica is a naturally occurring 2D mineral that has been heavily studied in many diverse areas. Here authors present atomic force microscopy images to study the mica surface in ultra-high vacuum conditions; they unveil the distribution of its surface K+ ions and give insights into the distribution of subsurface Al3+ ions.
- Giada Franceschi
- , Pavel Kocán
- & Ulrike Diebold
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Article
| Open AccessPQBP5/NOL10 maintains and anchors the nucleolus under physiological and osmotic stress conditions
The nucleolus is a liquid-liquid phase separation droplet that dynamically changes under stress. Here, the authors report PQBP5/NOL10 is a critical component of the nucleolus, maintaining its structure and position in the nucleus during osmotic stress.
- Xiaocen Jin
- , Hikari Tanaka
- & Hitoshi Okazawa
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Article
| Open AccessForce-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level
Combining high-speed AFM, single molecule recognition force spectroscopy, and molecular dynamics simulations Zhu, Canena, Sikora et al. characterize the interaction dynamics of the trimeric spike protein of SARS-CoV-2 wt, and delta and omicron variants with its entry receptor ACE2. While delta variant increases avidity by multivalent binding to ACE2, omicron variant shows an extended binding lifetime.
- Rong Zhu
- , Daniel Canena
- & Peter Hinterdorfer
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Article
| Open AccessMorphological control enables nanometer-scale dissection of cell-cell signaling complexes
Micropatterning on electron microscopy grids enables control of cell positioning and arrangement. Here, the authors describe detailed nanoscale characterization of a micropatterning workflow for reproducible molecular characterization through cryo-ET
- Liam P. Dow
- , Guido Gaietta
- & Dorit Hanein
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Article
| Open AccessAcousto-holographic reconstruction of whole-cell stiffness maps
Traditional methods for cell stiffness measurements are limited by long processing times and unsuitability for multiple cell analysis. Here, the authors demonstrate a fast technique based on acoustic stimulation and holographic imaging to reconstruct whole-cell stiffness maps of individual and multiple cells.
- Rahmetullah Varol
- , Zeynep Karavelioglu
- & Huseyin Uvet
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Comment
| Open AccessSeeing the unseen: High-resolution AFM imaging captures antibiotic action in bacterial membranes
Advances in atomic force microscopy (AFM) techniques and methodologies for microbiology contribute to our understanding of the microbial cell surface. Recent studies show that AFM imaging of cells and membranes at (near) molecular resolution allows detailed visualization of membranes interacting with drugs.
- Telmo O. Paiva
- , Albertus Viljoen
- & Yves F. Dufrêne
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Article
| Open AccessAntibiotic polymyxin arranges lipopolysaccharide into crystalline structures to solidify the bacterial membrane
Manioglu et al use high-resolution atomic force microscopy to resolve how polymyxins interact with the bacterial membrane. Polymyxins arrange the bacterial lipids into regular hexagonal structures that stiffen the membrane and lead to rupture.
- Selen Manioglu
- , Seyed Majed Modaresi
- & Sebastian Hiller
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Article
| Open AccessPerforin-2 clockwise hand-over-hand pre-pore to pore transition mechanism
Direct visualization of the structural transformation from pre-pore to pore of the mammalian immune defense complex perforin-2 (PFN2) reveals a clockwise hand-over-hand mechanism that propagates at ~15 subunits per second.
- Fang Jiao
- , François Dehez
- & Simon Scheuring
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Article
| Open AccessMultistep orthophosphate release tunes actomyosin energy transduction
Release of the ATP hydrolysis product orthophosphate (Pi) from the myosin active site is central in force generation but is poorly understood. Here, Moretto et al. present evidence for multistep Pi-release reconciling apparently contradictory results.
- Luisa Moretto
- , Marko Ušaj
- & Alf Månsson
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Article
| Open AccessNeurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19
Here the authors report the formation of toxic clumps of protein, similar to amyloid assemblies found in Alzheimer’s disease and suggest their possible role for some of the neurological symptoms of long-COVID.
- Mirren Charnley
- , Saba Islam
- & Nicholas P. Reynolds
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Article
| Open AccesspH- and concentration-dependent supramolecular assembly of a fungal defensin plectasin variant into helical non-amyloid fibrils
Here the authors report the cryo-EM structure of a triple-mutant of the anti-microbial peptide plectasin, PPI42, assembling in a pH- and concentration dependent manner into helical non-amyloid fibrils. The fibrils formation is reversible, and follows a sigmoidal kinetics. The fibrils adopt a right-handed helical superstructure composed by two protofilaments, stabilized by an outer hydrophobic ring and an inner hydrophobic centre. These findings reveal that α/β proteins can natively assemble into fibrils.
- Christin Pohl
- , Gregory Effantin
- & Pernille Harris
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Article
| Open AccessGasdermin-A3 pore formation propagates along variable pathways
Gasdermin-A3 pore formation propagates along diverse pathways. It begins with membrane attachment and oligomeric pre-assembly. Once inserted in the membrane, the oligomers re-assemble into various shapes and sizes, which open their lytic pores.
- Stefania A. Mari
- , Kristyna Pluhackova
- & Daniel J. Müller
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Article
| Open AccessStructural basis for the inhibition of IAPP fibril formation by the co-chaperonin prefoldin
Integrated kinetic and structural investigations reveal that the ubiquitous co-chaperonin prefoldin interacts with its coiled-coil helices on the islet amyloid polypeptide fibril surface and fibril ends to inhibit fibril elongation and secondary nucleation.
- Ricarda Törner
- , Tatsiana Kupreichyk
- & Jerome Boisbouvier
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Article
| Open AccessUnderstanding self-assembly at molecular level enables controlled design of DNA G-wires of different properties
G-wire structures have potential applications in bio-nanotechnology, however, this is limited by a lack of understanding about the assembly process and structures formed. Here, the authors use nuclear magnetic resonance and molecular dynamic simulations to understand the guiding principles of G-wire assembly.
- Daša Pavc
- , Nerea Sebastian
- & Primož Šket
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Article
| Open AccessSingle molecule kinetics of bacteriorhodopsin by HS-AFM
Here, the authors use high-speed atomic force microscopy (HS-AFM) methods to characterize the single molecule kinetics of wild-type bacteriorhodopsin (bR) with millisecond temporal resolution, providing new insights into the bR conformational cycle.
- Alma P. Perrino
- , Atsushi Miyagi
- & Simon Scheuring
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Article
| Open AccessMonitoring the binding and insertion of a single transmembrane protein by an insertase
The insertion and folding nascent or fully synthesized polypeptides into membranes is assisted by insertases. Here, the authors use a range of biophysical approaches to provide molecular details of how the transmembrane insertase YidC facilitates the insertion a protein into a phospholipid membrane.
- Pawel R. Laskowski
- , Kristyna Pluhackova
- & Daniel J. Müller
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Article
| Open AccessMolecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants
Here, the authors combine single-molecule atomic force spectroscopy measurements and molecular dynamics simulations to investigate the binding of spike proteins from four SARS-CoV-2 variants of concern (VoC) to the human ACE2 receptor. They observe an increase in the RBD-ACE2 complex stability for several of the VoCs and derive how the mutations affect the kinetic, thermodynamic and structural properties of complex formation.
- Melanie Koehler
- , Ankita Ray
- & David Alsteens
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Article
| Open AccessA blueprint of the topology and mechanics of the human ovary for next-generation bioengineering and diagnosis
Although the first dissection of the human ovary dates back to the 17th century, its characterization is still limited. Here, the authors have unraveled a unique biophysical and topological phenotype of reproductive-age tissue, bridging biophysics and female fertility and providing a blueprint for the artificial ovary.
- Emna Ouni
- , Alexis Peaucelle
- & Christiani A. Amorim
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Article
| Open AccessAn ester bond underlies the mechanical strength of a pathogen surface protein
Bacterial surface adhesion proteins are characterized by unusual mechanical properties. Here, the authors use atomic force microscopy-based technique to study a surface-anchoring protein Cpe0147 from Clostridium perfringens and show that an ester bond can withstand considerable mechanical forces and prevent complete protein unfolding.
- Hai Lei
- , Quan Ma
- & Yi Cao
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Article
| Open AccessCorrelation of membrane protein conformational and functional dynamics
High-speed atomic force microscopy height spectroscopy and single channel electrophysiology recordings are used to correlate conformational and functional dynamics of the model membrane protein, outer membrane protein G (OmpG). These techniques show that both states coexist and rapidly interchange in all conditions supported by molecular dynamics simulations.
- Raghavendar Reddy Sanganna Gari
- , Joel José Montalvo‐Acosta
- & Simon Scheuring
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Article
| Open AccessRheology of rounded mammalian cells over continuous high-frequencies
While rheology studies have contributed to the understanding of the viscoelastic properties of living cells, the use of higher frequencies promises elucidate the link between cellular and molecular properties. Here authors introduce a rheological assay that measures the cell mechanical response across a continuous frequency range ≈ 1 – 40 kHz.
- Gotthold Fläschner
- , Cosmin I. Roman
- & Daniel J. Müller
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Article
| Open AccessSynchronous RNA conformational changes trigger ordered phase transitions in crystals
Time-resolved crystallography (TRX) is used for monitoring only small conformational changes of biomacromolecules within the same lattice. Here, the authors report the interplay between synchronous molecular rearrangements and lattice phase transitions in RNA crystals, providing the basis for the investigation of large conformational changes using TRX.
- Saminathan Ramakrishnan
- , Jason R. Stagno
- & Yun-Xing Wang
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Article
| Open AccessInfrared nanospectroscopy reveals the molecular interaction fingerprint of an aggregation inhibitor with single Aβ42 oligomers
Our understanding of the molecular mechanisms underlying pathological protein aggregation remains incomplete. Here, single molecule infrared nanospectroscopy (AFM-IR) offers insight into the structure of Aβ42 oligomeric and fibrillar species and their interaction with an aggregation inhibitor, paving the way for single molecule drug discovery studies.
- Francesco Simone Ruggeri
- , Johnny Habchi
- & Tuomas P. J. Knowles
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Article
| Open AccessMassively parallel cantilever-free atomic force microscopy
Atomic force microscopy (AFM) provides high resolution, but is limited to small areas. Here, the authors introduce a massively parallel AFM approach with >1000 probes in a cantilever-free probe architecture, and present an optical method for detecting probe–sample contact with sub-10 nm vertical precision.
- Wenhan Cao
- , Nourin Alsharif
- & Keith A. Brown
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Article
| 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 AccessFibronectin-based nanomechanical biosensors to map 3D surface strains in live cells and tissue
The ability to measure strain in cells and tissues in vitro with minimal perturbation and at high spatial resolution has proven challenging. Here the authors develop a fluorescently-labelled fibronectin square lattice mesh that can be applied to the surface of cells and tissues to enable direct quantification and mapping of strain over time.
- Daniel J. Shiwarski
- , Joshua W. Tashman
- & Adam W. Feinberg
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Article
| Open Access3D-printed cellular tips for tuning fork atomic force microscopy in shear mode
The authors investigate 3D-printed tips, based on controlled microstructural architectured materials, as probes for shear-mode atomic force microscopy. They demonstrate that the tailored stiffness and energy-absorbing behaviour of the material are beneficial for improving image quality.
- Liangdong Sun
- , Hongcheng Gu
- & Zhongze Gu
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Article
| Open AccessThe hierarchical assembly of septins revealed by high-speed AFM
Septins are GTP-binding proteins involved in diverse cellular processes including division, polarity maintenance and membrane remodeling. Here authors use high-speed atomic force microscopy to show that assembly of septin filaments is a diffusion-driven process, while septin assembly into higher-order involves septin self-templating
- Fang Jiao
- , Kevin S. Cannon
- & Simon Scheuring
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Article
| Open AccessMillisecond dynamics of an unlabeled amino acid transporter
Excitatory amino acid transporters (EAATs) are crucial for the removal of excitatory amino acids from the synaptic cleft. Here authors combined high-speed atomic force microscopy line-scanning with automated state assignment for the determination of transport dynamics of GltPh, a prokaryotic EAAT homologue, with millisecond temporal resolution.
- Tina R. Matin
- , George R. Heath
- & Simon Scheuring
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Article
| Open AccessAssembly of a patchy protein into variable 2D lattices via tunable multiscale interactions
As nanoscale building blocks, proteins offer unique advantages, including monodispersity and atomically tunable interactions, but their self-assembly is limited compared to inorganic or polymeric nanoparticles. Here, the authors show modular self-assembly of an engineered protein into four physicochemically distinct patterned 2D crystals via control of four classes of interactions.
- Shuai Zhang
- , Robert G. Alberstein
- & F. Akif Tezcan
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Article
| Open AccessSingle molecule analysis reveals monomeric XPA bends DNA and undergoes episodic linear diffusion during damage search
It is not fully understood how XPA interacts with a DNA lesion during nucleotide excision repair. Here, the authors use single molecule analysis to study XPA–DNA interactions, including the DNA bend angle, protein stoichiometry, and diffusive properties during damage search.
- Emily C. Beckwitt
- , Sunbok Jang
- & Bennett Van Houten
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Article
| Open AccessSerial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade
Bacillus thuringiensis israelensis (Bti) produces the naturally-crystalline proteinaceous toxin Cyt1Aa that is toxic to mosquito larvae. Here the authors grow recombinant nanocrystals of the Cyt1Aa protoxin in vivo and use serial femtosecond crystallography to determine its structure at different redox and pH conditions and by combining their structural data with further biochemical, toxicological and biophysical analyses provide mechanistic insights into the Cyt1Aa bioactivation cascade.
- Guillaume Tetreau
- , Anne-Sophie Banneville
- & Jacques-Philippe Colletier
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Article
| Open AccessA biphasic growth model for cell pole elongation in mycobacteria
Mycobacteria grow by inserting new cell wall material at the cell poles. Here, Hannebelle et al. combine time-lapse optical and atomic force microscopy to show that single-cell growth is biphasic due to a lag phase of variable duration before the new pole transitions from slow to fast growth.
- Mélanie T. M. Hannebelle
- , Joëlle X. Y. Ven
- & Georg E. Fantner
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Article
| Open AccessRad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge
The Mre11/Rad50 complex, which functions in genome surveillance, possesses antiparallel coiled-coil arms forming a ring-like structure similar to that of the SMC family proteins. Here the authors find that the Rad50 zinc hook functions similarly to the hinge of the SMC protein, and that the ring structure of the Mre11/Rad50 dimer also opens by disconnecting its globular head domains.
- Hisashi Tatebe
- , Chew Theng Lim
- & Asako Furukohri
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Article
| Open AccessAnnexin-V stabilizes membrane defects by inducing lipid phase transition
Annexins are cytoplasmic proteins, which bind to membranes exposing negatively charged phospholipids in a Ca2+-dependent manner. Here the authors use high-speed atomic force microscopy and other techniques to show that annexin-V self-assembles into highly structured lattices that lead to a membrane phase transition on PS-rich membranes.
- Yi-Chih Lin
- , Christophe Chipot
- & Simon Scheuring
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Article
| Open AccessStructural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone
ATAD2 AAA+ ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, authors find that the fission yeast ATAD2 homolog Abo1 deposits histone H3–H4 onto DNA in an ATP-hydrolysis-dependent manner, and present the cryo-EM structure of an ATAD2 family ATPase to reveal the structural basis of nucleosome assembly by Abo1.
- Carol Cho
- , Juwon Jang
- & Ji-Joon Song
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Article
| Open AccessLipid order and charge protect killer T cells from accidental death
Cytotoxic T lymphocytes (CTLs) eliminate virus-infected and cancerous cells by secreting the pore-forming protein (perforin) and pro-apoptotic serine proteases (granzymes). Here authors show that two mechanisms protect the membranes of CTLs from disruption by perforin and granzymes.
- Jesse A. Rudd-Schmidt
- , Adrian W. Hodel
- & Ilia Voskoboinik
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Article
| Open AccessLocal Josephson vortex generation and manipulation with a Magnetic Force Microscope
Josephson vortices (JVs) play an important role in superconducting quantum devices, but they remain difficult to be observed and manipulated. Here, Dremov et al. report magnetic fingerprint of JVs in magnetic force microscopy experiments, which paves a way to generate and control JVs.
- Viacheslav V. Dremov
- , Sergey Yu. Grebenchuk
- & Vasily S. Stolyarov
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Article
| Open AccessEnzymatic biosynthesis and immobilization of polyprotein verified at the single-molecule level
Existing methods for protein polymer engineering suffer from low efficiency especially for synthesis large size polyproteins. Here, Deng et al. construct homo-polymer and co-polymer up to decamer by stepwise ligation and cleavage validated by atomic force microscopy-based single-molecule force spectroscopy.
- Yibing Deng
- , Tao Wu
- & Peng Zheng
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Article
| Open AccessSingle-molecule kinetics of pore assembly by the membrane attack complex
The membrane attack complex (MAC) is a hetero-oligomeric protein assembly that kills pathogens by perforating their cell envelopes. Here, the authors use atomic force microscopy to show that MAC proteins oligomerize within the membrane, allowing them to identify the kinetic bottleneck of MAC formation.
- Edward S. Parsons
- , George J. Stanley
- & Bart W. Hoogenboom