Single-molecule biophysics articles within Nature Communications

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  • Article
    | Open Access

    Biomarkers are natural indicators of some biological conditions, often used in diagnostics. Here, the authors developed a biosensor that continuously measures concentrations of DNA or protein biomarkers, and is based on particles that change mobility by directly interacting with individual molecules.

    • Emiel W. A. Visser
    • , Junhong Yan
    •  & Menno W. J. Prins

  • Article
    | Open Access

    Single molecule tracking of fluorescent proteins in live cells is temporally limited by fluorophore photobleaching. Here the authors show using fluorophore pairs that FRET competes with photobleaching to improve photostability and allow longer-term tracking of both single proteins and complexes.

    • Srinjan Basu
    • , Lisa-Maria Needham
    •  & Ernest D. Laue

  • Article
    | Open Access

    3D single-molecule localization is limited in depth and often requires using a wide range of point spread functions (PSFs). Here the authors present an optical solution featuring a deformable mirror to generate different PSFs and easy-to-use software for super-resolution imaging up to 5 µm deep.

    • Andrey Aristov
    • , Benoit Lelandais
    •  & Christophe Zimmer

  • Article
    | Open Access

    Existing methods to extract structural information from single-molecule scattering measurements require large number of photons per image. Here the authors discuss a method to reconstruct the structure of a molecule from X-ray scattering data by using only three photons per image.

    • Benjamin von Ardenne
    • , Martin Mechelke
    •  & Helmut Grubmüller

  • Article
    | Open Access

    During DNA replication, replicative helicases play an essential role for DNA unwinding to occur. Here the authors find that bacteriophage T7 helicase is also involved in replication re-initiation by interacting with a non-replicating DNAP and increasing unwinding rate.

    • Bo Sun
    • , Anupam Singh
    •  & Michelle D. Wang

  • Article
    | Open Access

    The bacterial protein disaggregation machine ClpB uses ATP to generate mechanical force to unfold and thread its protein substrates. Here authors visualize the ClpB ring using high-speed atomic force microscopy and capture conformational changes of the hexameric ring during the ATPase reaction.

    • Takayuki Uchihashi
    • , Yo-hei Watanabe
    •  & Toshio Ando

  • Article
    | Open Access

    Diffuse intrinsic pontine gliomas exhibit a characteristic mutation of lysine 27 to methionine (K27M) in genes encoding histone H3.3. Here the authors show that the H3.3K27M mutation imposes a specific pattern of H3.3K27 methylation by altering the target search dynamics of PcG proteins.

    • Roubina Tatavosian
    • , Huy Nguyen Duc
    •  & Xiaojun Ren

  • Article
    | Open Access

    Riboswitches on 5′ ends of mRNAs are important for bacterial gene regulation. Here the authors probe the mechanism of a tRNA aminoacylation sensing T-box riboswitch using single-molecule fluorescence microscopy to characterize dynamic solution conformations and heterogeneous tRNA binding kinetics.

    • Krishna C. Suddala
    • , Javier Cabello-Villegas
    •  & Nils G. Walter

  • Article
    | Open Access

    HIV particles contain a relatively low amount of viral envelope (Env), but underlying packaging mechanisms are poorly understood. Here, the authors use superresolution microscopy and show that Env distribution is biased toward the necks of cell-associated particles during assembly.

    • Carmen A. Buttler
    • , Nairi Pezeshkian
    •  & Schuyler B. van Engelenburg

  • Article
    | Open Access

    Evidence suggests oligomerisation of G protein-coupled receptors in membranes, but this is controversial. Here, authors use single-molecule and ensemble FRET, and spectroscopy to show that the neurotensin receptor 1 forms multiple dimer conformations that interconvert - “rolling” interfaces.

    • Patricia M. Dijkman
    • , Oliver K. Castell
    •  & Anthony Watts

  • Article
    | Open Access

    The bacterial transcription-repair coupling factor Mfd displaces stalled RNA polymerase (RNAP) by promoting transcription termination at sites of DNA lesions. Here the authors find—using single molecule imaging in live Escherichia coli—that RNAP stalls frequently during transcription, and needs to be rescued by Mfd during normal growth.

    • Han N. Ho
    • , Antoine M. van Oijen
    •  & Harshad Ghodke

  • Article
    | Open Access

    Polymer knots are important for a range of biological systems and engineering applications, yet the variables influencing knotting probability are not well understood. Here the authors develop a nanofluidic device that can detect knots and provide a free energy formalism that can quantify knotting probability in their system.

    • Susan Amin
    • , Ahmed Khorshid
    •  & Walter Reisner

  • Article
    | Open Access

    RNA synthesis by bacterial RNA polymerase is interrupted by pauses but their role in RNA synthesis is poorly understood. Here the authors use single-molecule FRET and biochemical analysis to show that pausing regulates branching between the abortive and productive outcomes of initial transcription.

    • David Dulin
    • , David L. V. Bauer
    •  & Achillefs N. Kapanidis

  • Article
    | Open Access

    The nucleolus is a membrane-less organelle formed through liquid–liquid phase separation (LLPS). Here the authors use biophysical methods and show that the nucleolar protein nucleophosmin (NPM1) also undergoes LLPS through homotypic, inter-NPM1 interactions and discuss implications for the ribosome biogenesis process.

    • Diana M. Mitrea
    • , Jaclyn A. Cika
    •  & Richard W. Kriwacki

  • Article
    | Open Access

    Mechanical properties of protein hydrogels are critical to mimic natural tissue but correlating bulk properties on the molecular level remains challenging. Here the authors show that the hierarchy of crosslinkers and load-bearing modules on a molecular level defines the mechanical properties of the hydrogel.

    • Junhua Wu
    • , Pengfei Li
    •  & Yi Cao

  • Article
    | Open Access

    The transport dynamics of messenger ribonucleoproteins in neurons is crucial to our neuronal functions, but the detail remains elusive. Song et al. show that they are transported along the dendrites in alternating run and rest phases with their own random sojourn times, following an aging Lévy walk.

    • Minho S. Song
    • , Hyungseok C. Moon
    •  & Hye Yoon Park

  • Article
    | Open Access

    Chromatin fibers undergo continuous structural rearrangements but their dynamic architecture is poorly understood. Here, the authors use single-molecule FRET to determine the structural states and interconversion kinetics of chromatin fibers, monitoring their effector protein-dependent dynamic motions.

    • Sinan Kilic
    • , Suren Felekyan
    •  & Beat Fierz

  • Article
    | Open Access

    Neurotransmitter:sodium symporters (NSS) modulate the duration and magnitude of signaling via the sodium-coupled reuptake of neurotransmitters. Here the authors describe quantitative single molecule imaging of ligand-induced, functional dynamics of both intracellular and extracellular surfaces of LeuT, further defining the mechanism for NSS transport.

    • Daniel S. Terry
    • , Rachel A. Kolster
    •  & Scott C. Blanchard

  • Article
    | Open Access

    The mechanics and structural transitions of DNA are important to many essential processes inside living cells. Here the authors combine theory and single-molecule experiments to show that intercalator binding stabilises a new structural state of DNA: hyperstretched DNA.

    • Koen Schakenraad
    • , Andreas S. Biebricher
    •  & Paul van der Schoot

  • Article
    | Open Access

    Existing methods for nanoscale visualization of biological targets in thick samples require complex hardware. Here, the authors combine the standard spinning disk confocal (SDC) microscopy with DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) to image proteins, DNA and RNA deep in cells.

    • Florian Schueder
    • , Juanita Lara-Gutiérrez
    •  & Ralf Jungmann

  • Article
    | Open Access

    Misfolding of superoxide dismutase 1 (SOD1) is linked to amyotrophic lateral sclerosis. Here the authors characterize the unfolding/refolding of single SOD1 molecules using optical tweezers, identifying partially folded intermediates that lead to misfolding after the formation of a native-like core.

    • Supratik Sen Mojumdar
    • , Zackary N. Scholl
    •  & Michael T. Woodside

  • Article
    | Open Access

    Formins are actin-polymerisation factors that are sensitive to force. Here the authors find that pulling force on an actin filament promoted faster actin polymerisation by the formin mDia1, and also found that the actin filament must be torsionally unconstrained, suggesting that mDia1 can also sense torque.

    • Miao Yu
    • , Xin Yuan
    •  & Jie Yan

  • Article
    | Open Access

    The effect of knots on protein stability and folding kinetics is not well understood. Here the authors combine optical tweezer experiments and calculations to experimentally determine the energy cost for knot formation, which indicates that knotted proteins evolved specific folding pathways because knot formation in unfolded chains is unfavorable.

    • Andrés Bustamante
    • , Juan Sotelo-Campos
    •  & Mauricio Báez

  • Article
    | Open Access

    It is still a challenge for current nanopore sensing methods to differentiate multiple analytes from complex biological material. Here, the authors graft nucleic acid aptamer sequences along the backbone of a double stranded DNA carrier for the detection of multiple protein targets in human serum.

    • Jasmine Y. Y. Sze
    • , Aleksandar P. Ivanov
    •  & Joshua B. Edel

  • Article
    | Open Access

    The GTP-bound form of initiation factor 2 (IF2) promotes translation initiation by accelerating 50S ribosomal subunit joining the 30S ribosomal initiation complex (30S IC). Here the authors use single-molecule FRET and ensemble rapid kinetic methods to uncover the mechanism behind IF2-mediated subunit joining.

    • Kelvin Caban
    • , Michael Pavlov
    •  & Ruben L. Gonzalez Jr

  • Article
    | Open Access

    While RNA folding is critical for its function, study of this process is challenging. Here, the authors combine nanopore single-molecule manipulation with theoretical analysis to follow the folding of an RNA pseudoknot, monitoring the intermediate states and the kinetics of their interconversion.

    • Xinyue Zhang
    • , Dong Zhang
    •  & Li-Qun Gu

  • Article
    | Open Access

    Contacts between RNA polymerase and promoter DNA modulate the strength of binding and the frequency of promoter escape during transcription. Here, the authors describe a single molecule optical-trapping assay to study transcription initiation and observe the dynamic remodeling of enzyme contacts in real time.

    • Cong A. Meng
    • , Furqan M. Fazal
    •  & Steven M. Block

  • Article
    | Open Access

    Understanding the role of enzymes in biomass depolymerization is essential for the development of more efficient biorefineries. Here, the authors show by atomic force microscopy the real-time mechanism of cellulose deconstruction by lytic polysaccharide monooxygenases.

    • Manuel Eibinger
    • , Jürgen Sattelkow
    •  & Bernd Nidetzky

  • Article
    | Open Access

    Forcing a DNA molecule into a nanoscale channel requires overcoming the free energy barrier associated with confinement. Here, the authors show that DNA injected through a funnel-shaped entrance more efficiently enters the nanochannel, thanks to facilitating forces generated by the nanofunnel geometry.

    • Jinsheng Zhou
    • , Yanqian Wang
    •  & J. Michael Ramsey

  • Article
    | Open Access

    Proteins fold under mechanical force during co-translational folding at the ribosome. Here, the authors use single molecule magnetic tweezers to study the influence of chaperones on protein folding and show that the ribosomal chaperone trigger factor acts as a mechanical foldase by promoting protein folding under force.

    • Shubhasis Haldar
    • , Rafael Tapia-Rojo
    •  & Julio M. Fernandez

  • Article
    | Open Access

    Efficient detection of single molecules is vital to many biosensing technologies, which require analytical platforms with high selectivity and sensitivity. Ren et al. combine a nanopore sensor and a field-effect transistor, whereby gate voltage mediates DNA and protein transport through the nanopore.

    • Ren Ren
    • , Yanjun Zhang
    •  & Yuri Korchev

  • Article
    | Open Access

    Ribosomes assemble through the hierarchical addition of proteins to a ribosomal RNA scaffold. Here the authors use three-color single-molecule FRET to show how the dynamics of the rRNA dictate the order in which multiple proteins assemble on the 5′ domain of the E. coli 16S rRNA.

    • Sanjaya C. Abeysirigunawardena
    • , Hajin Kim
    •  & Sarah A. Woodson

  • Article
    | Open Access

    The F508 deletion (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation. Here the authors show that cytosolic chaperones shift the F508del channel conformation to the native fold by kinetic and thermodynamic remodelling of the gating energetics towards that of wild-type CTFR.

    • Miklos Bagdany
    • , Guido Veit
    •  & Gergely L. Lukacs

  • Article
    | Open Access

    Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

    • Hongxia Fu
    • , Yan Jiang
    •  & Timothy A. Springer

  • Article
    | Open Access

    Both transcription binding kinetics and post-translational modifications of transcription factors are thought to play a role in the modulation of transcription. Here the authors use single-molecule tracking to directly demonstrate that p53 acetylation modulates promoter residence time and transcriptional activity.

    • Alessia Loffreda
    • , Emanuela Jacchetti
    •  & Davide Mazza

  • Article
    | Open Access

    Mapping the sequence specificity of DNA ligands remains a challenge, particularly for small drugs. Here the authors develop a parallelized single molecule magnetic tweezers approach using engineered DNA hairpins that can detect sequence selectivity, thermodynamics and kinetics of binding for small drugs and large proteins.

    • Maria Manosas
    • , Joan Camunas-Soler
    •  & Felix Ritort

  • Article
    | Open Access

    Multidrug efflux pumps significantly contribute for bacteria resistance to antibiotics. Here the authors present the structure of Campylobacter jejuni CmeB pump combined with functional FRET assays to propose a transport mechanism where each CmeB protomers is functionally independent from the trimer.

    • Chih-Chia Su
    • , Linxiang Yin
    •  & Edward W. Yu

  • Article
    | Open Access

    The contribution of ligands for cytokine receptor dimerization is still not fully understood. Here, the authors show the efficient ligand-induced dimerization of type II interleukin-4 receptor at the plasma membrane and the kinetic trapping of signalling complexes by actin-dependent membrane microdomains.

    • David Richter
    • , Ignacio Moraga
    •  & Jacob Piehler

  • Article
    | Open Access

    The permeabilization of the mitochondrial outer membrane to induce apoptosis is regulated by complex interactions between Bcl-2 family members. Here the authors develop a quantitative interactome of a membrane Bcl-2 network and identify a hierarchy of protein complexes in apoptosis induction.

    • Stephanie Bleicken
    • , Annika Hantusch
    •  & Ana J. Garcia-Saez

  • Article
    | Open Access

    Skeletal muscle myosin forms large ensembles to generate force against high loads. Using optical tweezers and simulation Kayaet al. provide experimental evidence for cooperative force generation, and describe how the molecular properties of skeletal myosins are tuned for coordinated power strokes.

    • Motoshi Kaya
    • , Yoshiaki Tani
    •  & Hideo Higuchi

  • Article
    | Open Access

    Transcription factors (TFs) are thought to regulate gene expression by stably binding to target DNA elements. Here, the authors use single-molecule tracking to analyse the dynamic behaviour of steroid receptors TFs and show that most specific interactions with chromatin are transient and dynamic.

    • Ville Paakinaho
    • , Diego M. Presman
    •  & Gordon L. Hager

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