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| Open Access4D analysis of malaria parasite invasion offers insights into erythrocyte membrane remodeling and parasitophorous vacuole formation
Here, Geoghegan, Evelyn et al. provide a lattice light-sheet microscopy based 4D imaging pipeline to quantitatively investigate Plasmodium spp. invasion and show that the nascent parasitophorous vacuole is predominantly formed from host’s erythrocyte membrane and undergoes continuous remodeling throughout invasion.
- Niall D. Geoghegan
- , Cindy Evelyn
- & Kelly L. Rogers
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Article
| Open AccessTight docking of membranes before fusion represents a metastable state with unique properties
Proteins need to overcome energy barriers to induce intermediate steps in membrane fusion. Using lipid vesicles in which progression to hemifusion is arrested, the authors show that the metastable intermediate is enhanced by divalent cations and is characterized by the absence of proteins and local membrane thickening. Simulations reveal that thickening is induced by dehydration of the membrane surface.
- Agata Witkowska
- , Leonard P. Heinz
- & Reinhard Jahn
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| Open AccessElectromechanical coupling mechanism for activation and inactivation of an HCN channel
Sea urchin hyperpolarization-activated cyclic nucleotide-gated (spHCN) ion channels channels are activated by membrane hyperpolarization instead of depolarization and undergo inactivation with hyperpolarization. Here authors apply transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels.
- Gucan Dai
- , Teresa K. Aman
- & William N. Zagotta
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Article
| Open AccessCohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel
A mutation in Shugoshin-1 causes the Chronic Atrial and Intestinal Dysrhythmia (CAID) Syndrome, but the underlying mechanisms are unknown. Here, the authors show that Shugoshin-1 controls cardiac pacemaker activity by interacting with HCN4 to enhance its cell-surface expression, and that the CAID-Syndrome mutation disrupts cardiac pacemaking by interfering with this important non-canonical interaction.
- Donghai Liu
- , Andrew Taehun Song
- & Stanley Nattel
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Article
| Open AccessReconstitution of contractile actomyosin rings in vesicles
Cytoskeletal networks support and direct cell shape and guide intercellular transport, but relatively little is understood about the self-organization of cytoskeletal components on the scale of an entire cell. Here, authors use an in vitro system and observe the assembly of different types of actin networks and the condensation of membrane-bound actin into single rings.
- Thomas Litschel
- , Charlotte F. Kelley
- & Petra Schwille
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Article
| Open AccessA self-organized synthetic morphogenic liposome responds with shape changes to local light cues
The authors generated a Synthetic Morphogenic Membrane System by encapsulating a dynamic microtubule aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized liposomes. This reconstitution of artificial proto-cells reveals how non-equilibrium phenomena affect cellular information processing in morphogenesis.
- Konstantin Gavriljuk
- , Bruno Scocozza
- & Philippe I. H. Bastiaens
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Article
| Open AccessAsymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers
Pentameric ligand-gated ion channels (pLGICs) are key players in neurotransmission and have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. Here, the authors report structures of the pLGIC 5-HT3A serotonin receptor reconstituted into lipid bilayer discs and reveal lipid–protein interactions as well as asymmetric activation of the homopentameric receptor.
- Yingyi Zhang
- , Patricia M. Dijkman
- & Mikhail Kudryashev
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Article
| Open AccessGating the pore of the calcium-activated chloride channel TMEM16A
The binding of cytoplasmic Ca2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck. Here authors use cryo-EM and electrophysiology to identify three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate.
- Andy K. M. Lam
- , Jan Rheinberger
- & Raimund Dutzler
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Article
| Open AccessMechanism of pore opening in the calcium-activated chloride channel TMEM16A
The anion channel TMEM16A is activated by intracellular Ca2+ in a highly cooperative process. Here authors combine electrophysiology and autocorrelation analysis to observe the sampling of intermediate conformations during gating.
- Andy K. M. Lam
- & Raimund Dutzler
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Article
| Open AccessStructures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization
Archaerhodopsin-3 (AR3) mutants are commonly used in optogenetics for neuron silencing and membrane voltage sensing. High-resolution crystal structures show that desensitization of the AR3 photoreceptor occurs when internal hydrogen-bonded water networks are modified in response to changes in chromophore isomerization.
- Juan F. Bada Juarez
- , Peter J. Judge
- & Anthony Watts
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Article
| Open AccessMechanism of membrane-curvature generation by ER-tubule shaping proteins
The endoplasmic reticulum network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs, but how they introduce curvature is poorly understood. Here authors show that REEPs form homodimers and use their amphipathic helix and trans-membrane segments to introduce high membrane curvature that can even lead to the formation of lipoprotein particles.
- Ning Wang
- , Lindsay D. Clark
- & Tom A. Rapoport
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Article
| Open AccessStructural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin
The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels. Here authors reveal the cryo-EM structure of LqhIII bound to NaV1.5 which shows that LqhIII traps the gating charges of the S4 segment in a unique intermediate-activated state and explains why LqhIII slows inactivation of NaV channels but does not open them.
- Daohua Jiang
- , Lige Tonggu
- & William A. Catterall
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Article
| Open AccessProlyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel
SthK, a cyclic nucleotide-gated ion channel from Spirochaeta thermophila activates slowly upon cAMP increase. Here, authors investigate cAMP-induced activation in purified SthK channels using stopped-flow assays and enzymatic catalysis and reveal that the cis/trans conformation of a conserved proline in the cyclic nucleotide-binding domain determines the activation kinetics of SthK.
- Philipp A. M. Schmidpeter
- , Jan Rheinberger
- & Crina M. Nimigean
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Article
| Open AccessGap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
Cell proliferation is regulated by cell volume, but it is unclear how individual cancer cells coordinate to regulate cell volumes in 3D clusters. Here the authors propose a mechano-osmotic model to analyse the exchange of fluid and ions between connected cells and their environment in response to proliferation-induced solid stress.
- Eoin McEvoy
- , Yu Long Han
- & Vivek B. Shenoy
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Article
| Open AccessAn expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo
The authors have previously reported split-GFP-based contact site sensors (SPLICS) to document endoplasmic reticulum/mitochondria contact sites. Here they extend this work and develop a range of improved SPLICS sensors to detect single and multiple organelle contact sites at different distances.
- Francesca Vallese
- , Cristina Catoni
- & Tito Calì
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Article
| Open AccessViral rhodopsins 1 are an unique family of light-gated cation channels
Nucleocytoplasmic Large DNA Viruses (NCLDV) that infect algae encode two distinct families of microbial rhodopsins. Here, the authors characterise two proteins form the viral rhodopsin group 1 OLPVR1 and VirChR1, present the 1.4 Å crystal structure of OLPVR1 and show that viral rhodopsins 1 are light-gated cation channels.
- Dmitrii Zabelskii
- , Alexey Alekseev
- & Valentin Gordeliy
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| Open AccessThe desensitization pathway of GABAA receptors, one subunit at a time
GABAA receptors mediate most inhibitory synaptic transmission in the brain. Here authors used concatemeric α1β2γ2 GABAA receptors to introduce gain-of-desensitization mutations one subunit at a time, revealing non-concerted rearrangements with a key contribution of the γ2 subunit during desensitization.
- Marc Gielen
- , Nathalie Barilone
- & Pierre-Jean Corringer
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Article
| Open AccessConnexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 Å
The local lipid environment is known to affect the structure, stability and intercellular channel activity of gap junctions, however, the molecular basis for these effects remains unknown. Here authors report the CryoEM structure of Cx46/50 lipid-embedded channels, by which they reveal a lipid-induced stabilization to the channel.
- Jonathan A. Flores
- , Bassam G. Haddad
- & Steve L. Reichow
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Article
| Open AccessDirected manipulation of membrane proteins by fluorescent magnetic nanoparticles
Membrane proteins are embedded in the lipid bilayer of the plasma membrane and their function in this context is often linked to their specific location and dynamics within the membrane. Here authors report the use of fluorescent magnetic nanoparticles to track membrane molecules and to manipulate their movement and pull membrane components laterally through the membrane with femtonewton-range forces.
- Jia Hui Li
- , Paula Santos-Otte
- & Helge Ewers
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Article
| Open AccessEvidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing
The TRPV1 ion channel is a heat-sensing receptor that is also activated by vanilloid compounds, but the molecular underpinnings of thermosensing have remained elusive. Here authors use in solution NMR on the isolated human TRPV1 S1-S4 domain and show that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity.
- Minjoo Kim
- , Nicholas J. Sisco
- & Wade D. Van Horn
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Article
| Open AccessTriacylglycerols sequester monotopic membrane proteins to lipid droplets
Triacylglycerols (TG) are synthesized at the endoplasmic reticulum (ER) bilayer and packaged into monolayer lipid droplets (LDs), but how proteins partition between ER and LDs is poorly understood. Here authors use synthetic model systems and find that proteins containing hydrophobic membrane association domains strongly prefer monolayers and that returning to the bilayer is unfavorable.
- Lucie Caillon
- , Vincent Nieto
- & Abdou Rachid Thiam
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Article
| Open AccessStructural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance
Mechanosensitive channels transduce physical force into electrochemical signaling in processes such as hearing, touch, proprioception, osmoregulation, and morphogenesis. Here, authors use cryo-electron microscopy to provide structural insights into the mechanical gating mechanism.
- Zengqin Deng
- , Grigory Maksaev
- & Peng Yuan
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Article
| Open AccessA dietary fatty acid counteracts neuronal mechanical sensitization
PIEZO2 is a critical component of the mechanism by which innocuous touch causes pain (tactile allodynia). Here, authors find that the dietary fatty acid margaric acid decreases PIEZO2 function in a dose-dependent manner and counteracts neuronal mechanical sensitization by a proalgesic agent.
- Luis O. Romero
- , Rebeca Caires
- & Valeria Vásquez
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| Open AccessHuman ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation
ESCRT-III complexes assemble in vivo inside membrane structures with a negative Gaussian curvature, but how membrane shape influences ESCRT-III polymerization remains unclear. Here authors use structural and biophysical methods to show how human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation.
- Aurélie Bertin
- , Nicola de Franceschi
- & Patricia Bassereau
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Article
| Open AccessBackmapping triangulated surfaces to coarse-grained membrane models
Computer simulations of large-scale changes in membrane shape are challenging since they occur across a wide range of spatiotemporal scales. Here, authors present a multiscale algorithm that backmaps a continuum membrane model represented as a dynamically triangulated surface to its corresponding molecular model based on the coarse-grained Martini force field.
- Weria Pezeshkian
- , Melanie König
- & Siewert J. Marrink
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| Open AccessMolecular mechanism of light-driven sodium pumping
The Na+-pumping KR2 rhodopsin from Krokinobacter eikastus is a light-driven non-proton cation pump whose mechanism of pumping remains to be understood. Here authors solved crystal structures of the O-intermediate state of the pentameric form of KR2 and its D116N and H30A mutants, which sheds light on the mechanism of non-proton cation light-driven pumping.
- Kirill Kovalev
- , Roman Astashkin
- & Valentin Gordeliy
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Article
| Open AccessControlled packing and single-droplet resolution of 3D-printed functional synthetic tissues
Precise patterning of lipid-stabilised aqueous droplets is a key challenge in building synthetic tissue designs. Here, the authors show how the interactions between pairs of droplets direct the packing of droplets within 3D-printed networks, enabling the formation of synthetic tissues with high-resolution features.
- Alessandro Alcinesio
- , Oliver J. Meacock
- & Hagan Bayley
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Article
| Open AccessLipoprotein Lpp regulates the mechanical properties of the E. coli cell envelope
Lipoprotein Lpp provides a covalent crosslink between the outer membrane and the peptidoglycan in E. coli. Here, the authors use atomic force microscopy to show that Lpp contributes to cell envelope stiffness by covalently connecting the two layers and by controlling the width of the periplasmic space.
- Marion Mathelié-Guinlet
- , Abir T. Asmar
- & Yves F. Dufrêne
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Article
| Open AccessGating mechanism of hyperpolarization-activated HCN pacemaker channels
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential for rhythmic activity in the heart and brain. Here authors reverse the voltage dependence of HCN channels by mutating only two residues located at the interface between the voltage sensor and the pore domain.
- Rosamary Ramentol
- , Marta E. Perez
- & H. Peter Larsson
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Article
| Open AccessLipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness
Proper membrane physiology requires maintenance of a narrow range of physicochemical properties, which must be buffered from external perturbations. Here, authors report lipidomic remodeling to preserve membrane physical properties upon exogenous polyunsaturated fatty acids exposure.
- Kandice R. Levental
- , Eric Malmberg
- & Ilya Levental
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Article
| Open AccessControlled division of cell-sized vesicles by low densities of membrane-bound proteins
Membrane fission of a cell into two daughters is a core ability of cell-based life. Here the authors show that in artificial cells division can be controlled by regulating membrane curvature using low protein density.
- Jan Steinkühler
- , Roland L. Knorr
- & Reinhard Lipowsky
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| Open AccessWhole-cell imaging of plasma membrane receptors by 3D lattice light-sheet dSTORM
The organisation of plasma membrane receptors is important for their function. Here the authors combine lattice light-sheet microscopy with 3D single-molecule localisation microscopy (dSTORM) and single-particle tracking to study the distribution and motility of several surface receptors.
- Felix Wäldchen
- , Jan Schlegel
- & Markus Sauer
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Article
| Open AccessTwo-stage electro–mechanical coupling of a KV channel in voltage-dependent activation
In voltage-gated potassium (KV) channels, the voltage-sensing domain (VSD) undergoes activation states to trigger pore opening via electro–mechanical (E–M) coupling. Here authors show that KV7.1 undergoes a two-stage E–M coupling mechanism during voltage-dependent activation.
- Panpan Hou
- , Po Wei Kang
- & Jianmin Cui
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Article
| Open AccessStructural basis of proton-coupled potassium transport in the KUP family
KUP transporters facilitate potassium uptake by the co-transport of protons and are key players in potassium homeostasis. Here authors identify the potassium importer KimA from Bacillus subtilis as a new member of the KUP transporter family and show the cryo-EM structure of KimA in an inward-occluded, trans-inhibited conformation.
- Igor Tascón
- , Joana S. Sousa
- & Inga Hänelt
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Article
| Open AccessThe C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus
Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide evidence for a toxic effector function in the gammaproteobacterium Serratia marcescens.
- Kathleen E. Orrell
- , Michael J. Mansfield
- & Roman A. Melnyk
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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 AccessDynamic constriction and fission of endoplasmic reticulum membranes by reticulon
The endoplasmic reticulum (ER) is an intracellular network characterized by highly dynamic behavior whose control mechanisms are unclear. Here, the authors show that the ER-membrane protein Reticulon (Rtnl1) can constrict ER bilayers and lead to ER fission.
- Javier Espadas
- , Diana Pendin
- & Andrea Daga
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Article
| Open AccessUnique structure and function of viral rhodopsins
Rhodopsin genes have been identified in some large double-stranded DNA viruses, but the structure and functions of viral rhodopsins remain unknown. Here authors present crystal structure and characterization of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII) which forms a pentamer and is a weak proton pump.
- Dmitry Bratanov
- , Kirill Kovalev
- & Valentin Gordeliy
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Article
| Open AccessPathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism
Mutations in the chloride channel ClC-2 have been found in primary aldosteronism (PA). Here, Göppner et al. generate transgenic mice expressing a mutant form of ClC-2 that displays increased chloride currents like patient mutations, and find it recapitulates the key pathological features of PA.
- Corinna Göppner
- , Ian J. Orozco
- & Thomas J. Jentsch
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Article
| Open AccessAllosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets
How mechanosensitive ion channels, such as MscL, are activated by lipids and physical properties of the membrane remains unclear. Here authors use PELDOR/DEER spectroscopy and identify a single site which generated an allosteric structural response in the absence of membrane tension.
- Charalampos Kapsalis
- , Bolin Wang
- & Christos Pliotas
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Article
| Open AccessStructure of the thermo-sensitive TRP channel TRP1 from the alga Chlamydomonas reinhardtii
Transient receptor potential (TRP) channels are ubiquitous occurring cation-selective sensory ion channels that respond to various stimuli. Here the authors characterize crTRP1 from the alga Chlamydomonas reinhardtii, present its 3.5 Å cryo-EM structure and show that crTRP1 opens in response to increased temperature and is positively regulated by the membrane lipid PIP2.
- Luke L. McGoldrick
- , Appu K. Singh
- & Alexander I. Sobolevsky
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Article
| Open AccessSolid-state NMR spectroscopy based atomistic view of a membrane protein unfolding pathway
Studying the unfolding of membrane proteins in a native-like lipid environment is challenging. Here the authors describe a method combining hydrogen-deuterium exchange and solid-state NMR measurements that allows the characterization of unfolding events in lipid-embedded membrane proteins and use the photoreceptor Anabaena Sensory Rhodopsin as a test case.
- Peng Xiao
- , David Bolton
- & Vladimir Ladizhansky
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Article
| Open AccessMolecular basis of PIP2-dependent regulation of the Ca2+-activated chloride channel TMEM16A
The calcium-activated chloride channel (CaCC) TMEM16A plays crucial roles in regulating neuronal excitability and muscle contraction. Here authors show that phosphatidylinositol (4,5)-bisphosphate (PIP2) regulates TMEM16A channel activation and desensitization via binding to a putative binding site.
- Son C. Le
- , Zhiguang Jia
- & Huanghe Yang
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Article
| Open AccessCa2+-regulated Ca2+ channels with an RCK gating ring control plant symbiotic associations
CASTOR is a Lotus japonicus ion channel required for nuclear Ca2+ spiking and establishing rhizobial and mycorrhizal symbioses. Here, via structural and functional analysis, Kim et al. show that CASTOR is a Ca2+-selective channel activated via Ca2+ binding to a soluble gating ring consisting of tandem RCK domains.
- Sunghoon Kim
- , Weizhong Zeng
- & Youxing Jiang
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Article
| Open AccessStudying nucleic envelope and plasma membrane mechanics of eukaryotic cells using confocal reflectance interferometric microscopy
Biomechanical studies of eukaryotic cells have been limited due to low sensitivity and axial resolution in interferometric imaging. Here, the authors present depth-resolved confocal reflectance interferometric microscopy with high sensitivity and temporal resolution, which enables quantification of nucleic envelope and plasma membrane fluctuations.
- Vijay Raj Singh
- , Yi An Yang
- & Peter T. C. So
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Article
| Open AccessControlling intercellular flow through mechanosensitive plasmodesmata nanopores
Plasmodesmata channels connect neighbouring plant cells and respond to external stimuli via changes in permeability. Here Park et al. propose that mechanical forces can displace the dumbbell-shaped ER-desmotubule complex that spans the central plasmodesmatal cylinder leading to closure of the pore.
- Keunhwan Park
- , Jan Knoblauch
- & Kaare H. Jensen
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Article
| Open AccessNoncanonical mechanism of voltage sensor coupling to pore revealed by tandem dimers of Shaker
Homotetrameric voltage-gated ion channels are assembled from individual subunits containing structurally distinct voltage sensor (VSD) and pore domains (PD). Here authors engineer tandem dimers of swapping-domains Shaker channels that allow distinguishing between VSD-to-PD far or near connections.
- João L. Carvalho-de-Souza
- & Francisco Bezanilla
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Article
| Open AccessReconstitution reveals how myosin-VI self-organises to generate a dynamic mechanism of membrane sculpting
Curvature-mediating proteins are known to induce specific membrane shapes, but whether motorprotein-lipid interactions remodel membranes too remains unclear. Here authors show that curvature-dependent lipid interactions of myosin-VI remodel the membrane geometry into dynamic spatial patterns.
- Benoit Rogez
- , Laeschkir Würthner
- & Claudia Veigel
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Article
| Open AccessDynamical nonlinear memory capacitance in biomimetic membranes
Two-terminal memory elements hold promise to store and process information via history-dependent material configurations at low-energy cost. Here, Najem et al. show a voltage-controlled capacitive memory due to reversible geometrical changes in a lipid bilayer capable of learning via synapse-like plasticity.
- Joseph S. Najem
- , Md Sakib Hasan
- & C. Patrick Collier