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| Open AccessStructural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB
KtrAB complex is essential in K+ uptake for bacteria. Here authors illustrate the synergism of ATP and Na+ in activating K+ uptake of KtrAB from Bacillus subtilis and its gating mechanism, which may also shed light on other Na+-activated K+ channels.
- Wesley Tien Chiang
- , Yao-Kai Chang
- & Nien-Jen Hu
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Article
| Open AccessIn situ captured antibacterial action of membrane-incising peptide lamellae
Inspired by the alternating chirality backbone pattern of some effective peptide antimicrobials, here authors design lysine-rich heterochiral peptides that show antimicrobial activity.
- Kamal el Battioui
- , Sohini Chakraborty
- & Tamás Beke-Somfai
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Article
| Open AccessLiquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection
The authors display the bottom-up design, assembly, and in-depth characterization of defined lipid-RNA structures in the core of lipid nanoparticles. The inverted structures are thermostable and provide better transfection over lamellar structures.
- Roy Pattipeiluhu
- , Ye Zeng
- & Thomas H. Sharp
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Article
| Open AccessExperimental determination and mathematical modeling of standard shapes of forming autophagosomes
Autophagosome formation involves membrane morphological changes. Here, authors statistically determined average shapes of forming autophagosomes from 3D electron micrographs and established a theoretical model that quantitatively reproduces them.
- Yuji Sakai
- , Satoru Takahashi
- & Noboru Mizushima
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Article
| Open AccessAcoustofluidic Interfaces for the Mechanobiological Secretome of MSCs
Efficient production of MSC secretome for therapeutic applications remains a challenging task. Here, the authors present an approach whereby an acoustofluidic mechanobiological environment can form reproducible 3D MSC aggregates, allowing for secretome production with high efficiency.
- Ye He
- , Shujie Yang
- & Tony Jun Huang
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Article
| Open AccessActivation and substrate specificity of the human P4-ATPase ATP8B1
Asymmetric phospholipid distribution in cell membranes is vital for cellular function. Here, authors reveal how ATP8B1, a P4-ATPase, can transport different lipids, including phosphatidylinositol.
- Thibaud Dieudonné
- , Felix Kümmerer
- & Poul Nissen
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Article
| Open AccessLocal membrane source gathering by p62 body drives autophagosome formation
Phase separated p62 body plays pivotal roles in autophagy. Here, the authors describe a spatial membrane gathering mode by which p62 body functions in autophagosome formation.
- Xuezhao Feng
- , Daxiao Sun
- & Na Mi
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Article
| Open AccessCryo-EM structures of human magnesium channel MRS2 reveal gating and regulatory mechanisms
Magnesium homeostasis is key for cellular functions. Here, authors report structures of human mitochondrial Mg2+ channel MRS2 and identified key residues in gating. This work provides insights into the gating and regulatory mechanisms of MRS2.
- Louis Tung Faat Lai
- , Jayashree Balaraman
- & Doreen Matthies
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Article
| Open AccessDirect regulation of the voltage sensor of HCN channels by membrane lipid compartmentalization
Voltage sensing of ion channels relies on charged transmembrane helices. Here authors use live-cell FLIM-FRET and nonsense suppression-mediated fluorescence labeling to reveal that voltage sensors undergo direct modulation by compartmentalized membrane domains.
- Lucas J. Handlin
- & Gucan Dai
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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 AccessMechanism of outer membrane destabilization by global reduction of protein content
The outer membrane (OM) of Gram-negative bacteria is an asymmetric bilayer, with phospholipids in the inner leaflet. Here the authors show that a reduction in OM proteins and the subsequent mislocalization of phospholipids weaken the OM and alter growth rate and cell shape, emphasizing the role of OM proteins in OM stiffness and cell shape.
- Irina V. Mikheyeva
- , Jiawei Sun
- & Thomas J. Silhavy
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Article
| Open AccessExperimental and theoretical model for the origin of coiling of cellular protrusions around fibers
The leading edges of cellular protrusions coil around extracellular fibers and other fibrous structures such as axons. Combining 3D imaging with theoretical models, the authors show that coiling occurs naturally on curved surfaces due to energy minimization.
- Raj Kumar Sadhu
- , Christian Hernandez-Padilla
- & Nir S. Gov
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Article
| Open AccessStructural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13
Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Here, the authors report crystal structures of HSD17B13 and its complexes with two series of inhibitors.
- Shenping Liu
- , Ruth F. Sommese
- & Michelle F. Clasquin
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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 AccessWetting and complex remodeling of membranes by biomolecular condensates
In this work, the authors investigated on the interaction of biomolecular condensates with membranes and report that they can exhibit two wetting transitions modulated by membrane or milieu composition. Condensate adhesion can trigger intriguing ruffling of the membrane interface into complex finger-like structures.
- Agustín Mangiarotti
- , Nannan Chen
- & Rumiana Dimova
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Article
| Open AccessLipid flipping in the omega-3 fatty-acid transporter
Lipid flipping across membrane leaflets are vital yet enigmatic biological processes. Here, five cryo-EM structures provide snapshots to delineate a mechanism of omega-3 fatty acid flipping across the blood brain barrier.
- Chi Nguyen
- , Hsiang-Ting Lei
- & Tamir Gonen
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Article
| Open AccessOligomeric scaffolding for curvature generation by ER tubule-forming proteins
How membranes are stretched and bent around the complex structures of cellular organelles is not fully understood. Xiang and colleagues report that endoplasmic reticulum tubule-forming proteins generate membrane curvature by constructing a curved oligomeric scaffold.
- Yun Xiang
- , Rui Lyu
- & Junjie Hu
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Article
| Open AccessStructure of the heterotrimeric membrane protein complex FtsB-FtsL-FtsQ of the bacterial divisome
The FtsB-FtsL-FtsQ complex is essential for regulating cell wall synthesis during bacterial cell division. Here, authors report the full-length trimeric structure showing a tilted V-shaped conformation and suggest an allosteric regulatory mechanism.
- Hong Thuy Vy Nguyen
- , Xiaorui Chen
- & Che Ma
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Article
| Open AccessStructural basis for TRIM72 oligomerization during membrane damage repair
TRIM72 oligomerization via intermolecular disulfide bonds is important for cells to repair damaged membranes. Here, authors report the crystal structure of TRIM72 dimer and show that TRIM72 B-box dimerization facilitates TRIM72 oligomerization.
- Yuemin Ma
- , Lei Ding
- & Chun Zhou
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Article
| Open AccessCholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols
Dumesnil et al. report that cholesterol esters (CE), which only melt above body temperature, form supercooled liquid crystalline lipid droplets (LD). Triacylglycerols (TG) solubilize CE to help CE LD nucleation. Through clustering TGs in the ER membrane, seipin controls CE LD nucleation sites.
- Calvin Dumesnil
- , Lauri Vanharanta
- & Abdou Rachid Thiam
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Article
| Open AccessThe cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex
The VTC complex generate eukaryotic polyphosphate (polyP). Authors here reveal how the signal-activated VTC synthesize cytosolic polyP and transport polyP across vacuolar membrane into the lumen, by using cryo-EM, in-cell NMR, and smFRET analyses.
- Zeyuan Guan
- , Juan Chen
- & Zhu Liu
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Article
| Open AccessRegions of hepatitis C virus E2 required for membrane association
Hepatitis C virus (HCV) uses a hybrid entry mechanism. Upon exposure to low pH, envelope glycoprotein E2 releases an internal loop into the host membrane. Here we show the amino terminal region is a critical determinant for membrane interaction, providing insights into the HCV entry mechanism.
- Ashish Kumar
- , Tiana C. Rohe
- & Joseph Marcotrigiano
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Article
| Open AccessStabilization of membrane topologies by proteinaceous remorin scaffolds
In plants, plasma membrane topologies are predominantly driven by the cell wall. In this study, the authors demonstrate that remorin proteins can take over these functions at specialized, unwalled plasma membranes such as infection droplets associated with symbiotic infection threads.
- Chao Su
- , Marta Rodriguez-Franco
- & Thomas Ott
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Article
| Open AccessThermodynamic architecture and conformational plasticity of GPCRs
GPCRs are integral membrane proteins that serve as attractive drug targets. Here, authors delineate the conformational landscapes of 45 GPCRs using a statistical model, highlighting their malleable native ensembles and providing functional insights.
- Sathvik Anantakrishnan
- & Athi N. Naganathan
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Article
| Open AccessMembrane curvature governs the distribution of Piezo1 in live cells
This study demonstrates that the curvature of the cell membrane directly regulates the spatial distribution of Piezo1, a widely expressed mechanosensitive ion channel. Piezo1 may flatten upon activation and can mechanically inhibit membrane dynamics
- Shilong Yang
- , Xinwen Miao
- & Zheng Shi
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Article
| Open AccessMembrane-mediated protein interactions drive membrane protein organization
High-Speed Atomic Force Microscopy movies of membrane proteins — diffusing and interacting in bilayers of controlled thickness — allow the determination of membrane-mediated membrane protein interaction energetics.
- Yining Jiang
- , Batiste Thienpont
- & Simon Scheuring
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Article
| Open AccessThe molecular organization of differentially curved caveolae indicates bendable structural units at the plasma membrane
Caveolae can bend and flatten, but how this is regulated is not well understood. Authors use correlative super-resolution light and electron microscopy to map the key proteins that mediate curvature of the caveolar coat.
- Claudia Matthaeus
- , Kem A. Sochacki
- & Justin W. Taraska
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Article
| Open AccessThe 3D structure of lipidic fibrils of α-synuclein
Interactions between α-synuclein fibrils and lipids have been associated with the development of Parkinson’s disease. This cryo-EM study reveals structural details of these interactions and suggests a mechanism for fibril-induced lipid extraction.
- Benedikt Frieg
- , Leif Antonschmidt
- & Gunnar F. Schröder
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Article
| Open AccessCrystal structure of the Na+/H+ antiporter NhaA at active pH reveals the mechanistic basis for pH sensing
By determining the crystal structure of the Na + /H + antiporter NhaA at active pH, the authors show how substrate accessibility to the ion-binding site can be controlled by pH sensitive switch located on the cytoplasmic surface.
- Iven Winkelmann
- , Povilas Uzdavinys
- & David Drew
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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 AccessStructural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA
PldA, a phospholipase D (PLD) effector, catalyzes hydrolysis of the phosphodiester bonds of glycerophospholipids—the main component of cell membranes—and assists the invasion of the opportunistic pathogen Pseudomonas aeruginosa. In this work, the authors report three intermediate structures of PldA by employing an integrated approach combining structural biology and biochemistry. Structural analysis reveals that the significant conformational changes in the “lid” region and the peripheral helical domain trigger the switch of the active pocket of PldA to regulate the enzymatic activity. The structure-based mutational experiments identified a series of key residues responsible for substrate hydrolysis activity and the interactions between PldA and PA3488. In summary, this work provides the structural basis for understanding the PldA-mediated invasion of P. aeruginosa and can aid the future drug development targeting PldA.
- Xiaoyun Yang
- , Zongqiang Li
- & Yanhua Li
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Article
| Open AccessAssembly of transmembrane pores from mirror-image peptides
Alpha-helix nanopores have a range of potential applications and the inclusion of non-natural amino acids allows for modification. Here, the authors report on the creation of alpha-helix pores using D-amino acids and show the pores formed, have different properties to the L-counterparts and were resistant to proteases.
- Smrithi Krishnan R
- , Kalyanashis Jana
- & Kozhinjampara R. Mahendran
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Article
| Open AccessStructure of an MHC I–tapasin–ERp57 editing complex defines chaperone promiscuity
Adaptive immunity depends on cellular chaperone and quality control systems that are decisive for an effective presentation of foreign antigens via MHC I molecules. Here, the authors present the structure of a key chaperone-MHC I complex.
- Ines Katharina Müller
- , Christian Winter
- & Robert Tampé
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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 AccessVisualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery
Membrane fusion is essential for cellular entry of enveloped viruses. Here, authors use time-resolved cryo-electron tomography and subtomogram averaging to capture 3D organization and population evolution of intermediates during membrane fusion of CHIKV, a medically important alphavirus.
- Vidya Mangala Prasad
- , Jelle S. Blijleven
- & Kelly K. Lee
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Article
| Open AccessBuilding programmable multicompartment artificial cells incorporating remotely activated protein channels using microfluidics and acoustic levitation
Engineering micro-emulsion plays a key role in the creation of bottom-up synthetic cells. Here, authors demonstrate a droplet laboratory platform to control membrane protein gating in functional artificial cell using microfluidics and acoustic levitation.
- Jin Li
- , William D. Jamieson
- & David A. Barrow
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Article
| Open AccessCryo-EM structure of human glucose transporter GLUT4
Small solute carriers remain difficult to study by single particle cryo-EM. Here, the authors report the cryo-EM structure of human insulin-responsive glucose transporter GLUT4 (55 kDa) without rigid soluble domains or binders.
- Yafei Yuan
- , Fang Kong
- & Chuangye Yan
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Article
| Open AccessPeptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients
Bacterial cell wall enzymes and their precursors are critical targets for antibiotic development. Here, the authors investigate several biosynthetic enzymes with their substrates and show that the passage of substrates and products in the pathway is controlled by their relative binding affinities.
- Abraham O. Oluwole
- , Robin A. Corey
- & Carol V. Robinson
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Article
| Open AccessTunable and scalable fabrication of block copolymer-based 3D polymorphic artificial cell membrane array
In this manuscript, an electric-field-assisted self-assembly technique that can allow controllable and scalable fabrication of 3-dimensional block copolymer (BCP)-based artificial cell membranes (3DBCPMs) immobilized on predefined locations is presented.
Topographically and chemically structured microwell array templates facilitate uniform patterning of BCPs and serve as reactors for the effective growth of 3DBCPMs, which diverse shapes, sizes and stability can be tuned by modulating the BCP concentration and the amplitude/frequency of the electric field.
The potential of 3DBCPMs for a variety of biological applications is highlighted by performance of in vitro protein-membrane assays and mimicking of human intestinal organs.
- Dong-Hyun Kang
- , Won Bae Han
- & Tae Song Kim
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Article
| Open AccessA polytherapy based approach to combat antimicrobial resistance using cubosomes
An increasing prevalence of Gram-negative bacteria increases the interest in nanotherapies to treat antibiotic resistance. Here, the authors examine the antimicrobial activity of polymyxin-loaded cubosomes and explore a polytherapy treatment of pathogens with cubosomes in combination with polymyxin.
- Xiangfeng Lai
- , Mei-Ling Han
- & Hsin-Hui Shen
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Article
| Open AccessOne-step construction of circularized nanodiscs using SpyCatcher-SpyTag
Circularised nanodiscs (cNDs) are able to stabilise large lipid bilayer patches and are used for structural and functional studies. Current techniques to build cNDs have numerous steps and low yields; here the authors report a single step construction method using the SpyCatcher-SpyTag system.
- Shanwen Zhang
- , Qian Ren
- & Huan Bao
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Article
| Open AccessEn route to dynamic life processes by SNARE-mediated fusion of polymer and hybrid membranes
A variety of artificial cells springs from the functionalization of liposomes with proteins but these models suffer from low durability without repair and replenishment mechanisms. Here, the authors show that synthetic amphiphile membranes undergo SNARE-mediated fusion, and determine bending rigidity and pore edge tension as key parameters for fusion.
- Lado Otrin
- , Agata Witkowska
- & Tanja Vidaković-Koch
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Article
| Open AccessThe role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding
The folding of outer membrane proteins (OMPs) is catalyzed by the βbarrel assembly machinery (BAM). Here, structural and functional analyses of BAM stabilized in distinct conformations elucidate the roles of lateral gate opening and interactions of BAM with the lipid bilayer in OMP assembly.
- Paul White
- , Samuel F. Haysom
- & Sheena E. Radford
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Article
| Open AccessCeramide structure dictates glycosphingolipid nanodomain assembly and function
Gangliosides such as GM1 present in the outer leaflet of the plasma membrane of eukaryotic cells are essential for many cellular functions and pathogenic interactions. Here the authors show that the acyl chain structure of GM1 determines the establishment of nanodomains when actively clustered by actin, which depended on membrane cholesterol and phosphatidylserine or superimposed by the GM1-binding bacterial cholera toxin.
- Senthil Arumugam
- , Stefanie Schmieder
- & Ludger Johannes
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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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Article
| Open AccessProbing the biogenesis pathway and dynamics of thylakoid membranes
Cyanobacterial thylakoid membranes host the molecular machinery for the light-dependent reactions of photosynthesis and respiratory electron flow. Here, the authors show that newly synthesized thylakoids emerge between the plasma membrane and pre-existing thylakoids and describe the time-dependent assembly process of photosynthetic complexes.
- Tuomas Huokko
- , Tao Ni
- & Lu-Ning Liu
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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 AccessSTIM-Orai1 signaling regulates fluidity of cytoplasm during membrane blebbing
The cytoplasm in mammalian cells is considered homogeneous. Here authors report that the cytoplasmic fluidity is regulated in the blebbing cells, which is regulated by calcium concentration in the expanding blebs and involves the STIM-Orai1 pathway.
- Kana Aoki
- , Shota Harada
- & Junichi Ikenouchi
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Article
| Open AccessNanoscale imaging of bacterial infections by sphingolipid expansion microscopy
Imaging of lipid bilayers using light microscopy is challenging. Here the authors label cells using a short chain click-compatible ceramide to visualize mammalian and bacterial membranes with expansion microscopy.
- Ralph Götz
- , Tobias C. Kunz
- & Markus Sauer