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Article
| Open AccessThe actin cytoskeleton plays multiple roles in structural colour formation in butterfly wing scales
NCOMMS-23-44446C Vivid structural colours in butterflies are caused by photonic nanostructures scattering light, however insight into the development of such structures in vivo remains scarce. Here the authors show that actin plays a vital and direct templating role during structural colour formation in butterfly scales, providing ridge patterning mechanisms that are likely universal across lepidoptera.
- Victoria J. Lloyd
- , Stephanie L. Burg
- & Andrew J. Parnell
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Article
| Open AccessAn optofluidic antenna for enhancing the sensitivity of single-emitter measurements
Single molecule investigations are often performed in fluidic environments, but molecular diffusion and limited photon counts can compromise studies of processes with fast or slow dynamics. The authors introduce a planar optofluidic antenna which enhances the fluorescence signal from molecules, applicable to a diverse range of studies.
- Luis Morales-Inostroza
- , Julian Folz
- & Vahid Sandoghdar
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Article
| Open AccessMyriad Mapping of nanoscale minerals reveals calcium carbonate hemihydrate in forming nacre and coral biominerals
A new carbonate phase calcium carbonate hemihydrate was recently discovered and characterized, but exclusively as a synthetic material. Here the authors find that it exists in nature, albeit transiently, on the surface of growing nacre and coral skeletons, and show that 2 amorphous and 2 metastable crystalline nano-minerals form before biominerals settle into their stable crystals.
- Connor A. Schmidt
- , Eric Tambutté
- & Pupa U.P.A. Gilbert
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Article
| Open AccessMonitoring the mass, eigenfrequency, and quality factor of mammalian cells
There is increasing interest in measuring the mechanical properties of living cells. Here, the authors develop a method to simultaneously measure the cell mass and two parameters related to its natural oscillation or resonance frequencies.
- Sophie Herzog
- , Gotthold Fläschner
- & Daniel J. Müller
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Article
| 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 AccessBlue-shift photoconversion of near-infrared fluorescent proteins for labeling and tracking in living cells and organisms
Photolabeling of intracellular molecules is an invaluable approach to study multiple cellular processes. Here, the authors report on the near-infrared to far-red photoconversion in the miRFP family of fluorescent proteins, which enables photolabeling entirely performed in the near-infrared range.
- Francesca Pennacchietti
- , Jonatan Alvelid
- & Ilaria Testa
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Article
| Open AccessCytosolic actin isoforms form networks with different rheological properties that indicate specific biological function
β-actin and γ-actin are nearly identical, and yet incorporate into different cytoskeletal structures. Here, the authors create isoform-pure reconstituted networks and study their structural and mechanical differences, underscoring the significance of the isoforms in diverse cellular functions.
- Peter Nietmann
- , Kevin Kaub
- & Andreas Janshoff
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Article
| Open AccessChemo-mechanical forces modulate the topology dynamics of mesoscale DNA assemblies
Understanding the topological arrangement and transition dynamics of mesoscale assemblies is complicated by their molecular complexity. Here, the authors use DNA origami nanosprings to show that mesoscale helical handedness is dictated by backbone torque rather than achiral orientation.
- Deepak Karna
- , Eriko Mano
- & Hanbin Mao
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Article
| Open AccessBiomolecular condensates modulate membrane lipid packing and hydration
Nano-environmental probes and advance imaging microscopy provide deep insight into protein phase separation and the interaction of condensates with membranes, revealing that wetting by condensates can modulate membrane lipid packing and hydration.
- Agustín Mangiarotti
- , Macarena Siri
- & Rumiana Dimova
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Article
| Open AccessExploring non-equilibrium processes and spatio-temporal scaling laws in heated egg yolk using coherent X-rays
The soft-grainy microstructure of cooked egg yolk is the result of a series of out of equilibrium processes of its protein-lipid contents. Here, the authors develop a time-temperature phase diagram that shows the coupling of the nanoscale processes that result in the grainy-gel microstructure of cooked egg yolk.
- Nimmi Das Anthuparambil
- , Anita Girelli
- & Christian Gutt
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Article
| Open AccessBuilding block aspect ratio controls assembly, architecture, and mechanics of synthetic and natural protein networks
Fibrous networks constructed from high aspect ratio protein building blocks are ubiquitous in nature, but the functional advantage of such building blocks over globular proteins is not understood. Here, using shear rheology and small-angle neutron scattering, the authors characterise the mechanical and structural properties of photochemically crosslinked protein L and fibrin networks and show that aspect ratio is a crucial property that defines network architecture and mechanics.
- Matt D. G. Hughes
- , Sophie Cussons
- & Lorna Dougan
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Article
| Open AccessStable trapping of multiple proteins at physiological conditions using nanoscale chambers with macromolecular gates
The possibility to trap biomolecules is important for analysing them by optical methods. Here we show how nanoscale chambers with macromolecular gates can be used to trap hundreds of proteins in a volume of one attoliter at physiological conditions without exposing them to any direct forces.
- Justas Svirelis
- , Zeynep Adali
- & Andreas Dahlin
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Matters Arising
| Open AccessAntibiotics and hexagonal order in the bacterial outer membrane
- Georgina Benn
- , Thomas J. Silhavy
- & Bart W. Hoogenboom
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Article
| Open AccessStructure and proposed DNA delivery mechanism of a marine roseophage
Tailed bacteriophages account for the majority of all phages. Here, the authors employ cryo-EM and structure prediction techniques to investigate the atomic structure of the R4C phage capsid and the in- situ structure of its unique long rigid tail.
- Yang Huang
- , Hui Sun
- & Ningshao Xia
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Article
| Open AccessAntibody binding reports spatial heterogeneities in cell membrane organization
The organization of proteins and sugars on the cell membrane is crucial for cell signaling and function. Here, authors develop molecular probes and simulations to characterize the spatial organization of macromoleucles on live cell membranes.
- Daniel P. Arnold
- , Yaxin Xu
- & Sho C. Takatori
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Article
| Open AccessAutophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription
An autophagy receptor, NDP52, is recruited to the nucleus where it can bind DNA. The authors show this promotes changes in chromatin accessibility which supports transcription initiation, providing a direct link between autophagy and transcription regulation.
- Ália dos Santos
- , Daniel E. Rollins
- & Christopher P. Toseland
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Article
| Open AccessSiglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket
Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer. Here, the authors combine a variety of chemical biology techniques to demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.
- Edward N. Schmidt
- , Dimitra Lamprinaki
- & Matthew S. Macauley
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Article
| Open AccessCollagen breaks at weak sacrificial bonds taming its mechanoradicals
Collagen is an important structural protein in connective tissue, but the effect of location and type of micro-ruptures in the structure on the overall tissue is not well understood. Here, the authors use scale-bridging simulations to determine the breakage points in collagen, and how the failure mode helps to prevent material ageing
- Benedikt Rennekamp
- , Christoph Karfusehr
- & Frauke Gräter
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Article
| Open AccessSingle-molecule localization microscopy reveals the ultrastructural constitution of distal appendages in expanded mammalian centrioles
The authors have combined direct stochastic optical reconstruction microscopy with expansion microscopy to describe the 3-dimensional molecular organization of centriolar distal appendages.
- Ting-Jui Ben Chang
- , Jimmy Ching-Cheng Hsu
- & T. Tony Yang
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Article
| Open AccessSpatially confined protein assembly in hierarchical mesoporous metal-organic framework
Immobilization of biomolecules into porous materials could lead to enhanced performance in terms of stability and easier separation for their reuse. Here authors gain insights into the spatial arrangement of green fluorescent protein entrapped in a mesoporous MOF by situ small-angle neutron scattering.
- Xiaoliang Wang
- , Lilin He
- & Shengqian Ma
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Article
| Open AccessPhosphorylation disrupts long-distance electron transport in cytochrome c
Electron transfer between mitochondrial cytochrome c and subunit of cytochrome bc1 can proceed at long distance. Here the authors investigate further the mechanism and show phosphorylation regulation of the interactions between the protein partners in the electron transport chain.
- Alexandre M. J. Gomila
- , Gonzalo Pérez-Mejías
- & Anna Lagunas
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Article
| Open AccessIn situ small-angle X-ray scattering reveals strong condensation of DNA origami during silicification
DNA origami can be coated in a layer of silica to improve chemical and thermal stability however; it is unclear if this is a surface or interpenetrating layer. Here, the authors use in situ small-angle X-ray scattering to study silica deposition and observe internal silica formation resulting in DNA origami condensation and structure shrinkage.
- Martina F. Ober
- , Anna Baptist
- & Bert Nickel
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Article
| Open AccessResolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses
The European X-ray FreeElectron Laser Facility generates ultrashort hard X-ray pulses with megahertz repetition rate. Here, the authors probe the dynamics of dense antibody protein (Ig-PEG) solutions using megahertz X-ray photon correlation spectroscopy at the European XFEL.
- Mario Reiser
- , Anita Girelli
- & Christian Gutt
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Article
| Open AccessPercolation transition prescribes protein size-specific barrier to passive transport through the nuclear pore complex
Combining realistic coarse-grained simulations with a percolation transition theory, this study elucidates the microscopic mechanism that governs the selectivity of passive, unassisted transport through the nuclear pore complex.
- David Winogradoff
- , Han-Yi Chou
- & Aleksei Aksimentiev
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Article
| Open AccessSingle-droplet surface-enhanced Raman scattering decodes the molecular determinants of liquid-liquid phase separation
The authors introduce a unique single-droplet surface-enhanced Raman scattering (SERS) methodology that illuminates a wealth of molecular information within the mesoscopic liquid condensed phase of Fused in Sarcoma in the absence and presence of RNA.
- Anamika Avni
- , Ashish Joshi
- & Samrat Mukhopadhyay
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Article
| Open AccessA modular spring-loaded actuator for mechanical activation of membrane proteins
Studies on mechanotransduction are limited by our ability to apply low range forces to specific mechanoreceptors on cell membranes. Here the authors report the Nano-winch, a programmable DNA origami-based molecular actuator, to manipulate multiple mechanoreceptors in parallel by exerting piconewton forces.
- A. Mills
- , N. Aissaoui
- & G. Bellot
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Article
| Open AccessTopological digestion drives time-varying rheology of entangled DNA fluids
Understanding and controlling the rheology of polymeric complex fluids is of fundamental importance in both industry and biology. Here, Michieletto et al. show how to achieve time-dependent rheology of DNA solutions via enzymatically-driven architectural alterations by restriction endonucleases.
- D. Michieletto
- , P. Neill
- & R. M. Robertson-Anderson
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Article
| Open AccessNanoscale regulation of Ca2+ dependent phase transitions and real-time dynamics of SAP97/hDLG
SAP97/hDLG is a ubiquitous, alternatively spliced, and conserved modular scaffolding protein involved in the organization cell junctions and excitatory synapses. Here, authors confirm that SAP97/hDLG condenses in to nanosized molecular domains in both heterologous cells and hippocampal pyramidal neurons. Authors demonstrate that in vivo and in vitro condensation, molecular signatures of nanoscale condensates and exchange kinetics of SAP97/hDLG is modulated by the local availability of alternatively spliced isoforms. Additionally, SAP97/hDLG isoforms exhibits a differential sensitivity to Ca2+ bound Calmodulin, resulting in altered properties of nanocondensates and their real-time regulation
- Premchand Rajeev
- , Nivedita Singh
- & Deepak Nair
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Article
| Open AccessNanoscale organization of two-dimensional multimeric pMHC reagents with DNA origami for CD8+ T cell detection
MHC-peptide multimers are important reagents for detecting antigen specific T cells. Here the authors show that DNA scaffolds can be used to make MHC-peptide multimers and the avidity controlled so that low abundance or T cells with low affinity TCR can be detected using these reagents.
- Yueyang Sun
- , Lu Yan
- & Hao Pei
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Article
| Open AccessElasticity of podosome actin networks produces nanonewton protrusive forces
Actin filaments generate force in diverse contexts, although how they can produce nanonewtons of force is unclear. Here, the authors apply cryo-electron tomography, quantitative analysis, and modelling to reveal the podosome core is a dense, spring-loaded, actin network storing elastic energy.
- Marion Jasnin
- , Jordan Hervy
- & Renaud Poincloux
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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 AccessThe influence of Holliday junction sequence and dynamics on DNA crystal self-assembly
Engineered crystal architectures from DNA have become a foundational goal for nanotechnological precise arrangement. Here, the authors systematically investigate the structures of 36 immobile Holliday junction sequences and identify the features allowing the crystallisation of most of them, while 6 are considered fatal.
- Chad R. Simmons
- , Tara MacCulloch
- & Hao Yan
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Article
| Open AccessMembrane curvature regulates the spatial distribution of bulky glycoproteins
MUC1 is a heavily glycosylated protein on the cell surface. Here the authors show that MUC1 prefers negative over positive membrane curvature due to its bulky size, enabling MUC1 to avoid endocytosis and surface removal based on curvature preference.
- Chih-Hao Lu
- , Kayvon Pedram
- & Bianxiao Cui
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Article
| Open AccessOn the origins of conductive pulse sensing inside a nanopore
Conductive events during nanopore sensing, are seen typically under low salt conditions and widely thought to arise from counterions brought into the pore via analyte. Here, authors show that an imbalance of ionic fluxes lead to conductive events.
- Lauren S. Lastra
- , Y. M. Nuwan D. Y. Bandara
- & Kevin J. Freedman
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Article
| Open AccessMultivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection
Cell surface attachment factors, such as glycans, play an important role in viral infection. Here, Petitjean et al. show that SARS-CoV-2 specifically binds to 9-Oacetylated sialic acid and have designed novel inhibitors based on multivalent derivatives.
- Simon J. L. Petitjean
- , Wenzhang Chen
- & David Alsteens
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Article
| Open AccessA reversibly gated protein-transporting membrane channel made of DNA
Artificial systems to control the transport of molecules across biomembranes can be useful for biosensing or drug delivery. Here, the authors assemble a DNA channel enabling the precisely timed, stimulus-controlled transport of functional proteins across bilayer membranes.
- Swarup Dey
- , Adam Dorey
- & Hao Yan
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Article
| Open Access100 Hz ROCS microscopy correlated with fluorescence reveals cellular dynamics on different spatiotemporal scales
In live-cell microscopy, motion blur limits resolution and contrast. Here the authors use 100 Hz super-resolving Rotating Coherent Scattering (ROCS) microscopy on various dynamic biological systems, and time-window analysis to understand biological effects.
- Felix Jünger
- , Dominic Ruh
- & Alexander Rohrbach
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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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Article
| 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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Article
| Open AccessMyosin VI regulates the spatial organisation of mammalian transcription initiation
The actin-based molecular motors, myosins, have also been linked to transcription, but their precise role has remained elusive. Here the authors show RNA polymerase II (RNAPII) is lost from chromatin upon myosin perturbation and that myosin acts as a molecular anchor to maintain RNAPII spatial organisation.
- Yukti Hari-Gupta
- , Natalia Fili
- & Christopher P. Toseland
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Article
| Open AccessDisentangling the recognition complexity of a protein hub using a nanopore
Nanopores are powerful tools for sampling protein-peptide interactions. Here, the authors convert a protein-based nanopore into a sensitive biosensor to characterize the complex binding of WDR5 protein to a 14-residue ligand.
- Lauren Ashley Mayse
- , Ali Imran
- & Liviu Movileanu
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Article
| Open AccessData-informed discovery of hydrolytic nanozymes
Developing hydrolytic nanozymes remains challenging. Here the authors present a rational methodology to design hydrolytic nanozyme by developing a data-informed strategy to screen and identify potential scaffold and active sites of hydrolase-like nanozyme.
- Sirong Li
- , Zijun Zhou
- & Hui Wei
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Article
| Open AccessHydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures
Developing antibacterial agents which don’t have cytotoxic effects against mammalian cells is of interest for biomedical applications. Here, the authors explore how attaching inert polymer brushes to different sized nanoparticles can result in toxicity to bacteria but not to mammalian cells in a size dependent manner.
- Yunjiang Jiang
- , Wan Zheng
- & Hongjun Liang
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Article
| Open AccessResonator nanophotonic standing-wave array trap for single-molecule manipulation and measurement
Applications of nanophotonic tweezers have been limited by the low trapping force. Here, the authors present enhanced force generation in a nanophotonic standing-wave array trap by integrating a critically-coupled resonator design and demonstrate common single-molecule experiments.
- Fan Ye
- , James T. Inman
- & Michelle D. Wang
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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 AccessDigital immunoassay for biomarker concentration quantification using solid-state nanopores
The concentration of a biomarker in solution can be determined by counting single molecules. Here the authors report a digital immunoassay scheme with solid-state nanopore readout to quantify a target protein and use this to measure thyroid-stimulating hormone from human serum.
- Liqun He
- , Daniel R. Tessier
- & Vincent Tabard-Cossa
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Article
| Open AccessTurn-key mapping of cell receptor force orientation and magnitude using a commercial structured illumination microscope
The authors have recently developed molecular force microscopy (MFM) which uses fluorescence polarisation to measure cell-surface receptor force orientation. Here they show that structured illumination microscopes, which inherently use fluorescence polarisation, can be used for MFM in a turn-key manner.
- Aaron Blanchard
- , J. Dale Combs
- & Khalid Salaita
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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 AccessOptoregulated force application to cellular receptors using molecular motors
Molecular scale force application in physiological environments is important for studying mechanotransduction. Here, the authors use a molecular machine to apply forces at cell-matrix and cell-cell junctions using light to trigger twisting actuation which then pulls on cell membrane receptors.
- Yijun Zheng
- , Mitchell K. L. Han
- & Aránzazu del Campo