Featured
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Perspective |
Challenges and opportunities in achieving the full potential of droplet interface bilayers
Droplet interface bilayers (DIBs) are a type of artificial bilayer that can act as cell membrane mimics. This Perspective surveys how DIBs can be used to mimic key cellular features (such as bilayer asymmetry) and processes (such as drug movement), and discusses challenges that need to be overcome to enable DIBs to reach their full potential as biomimetic model membranes.
- Elanna B. Stephenson
- , Jaime L. Korner
- & Katherine S. Elvira
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Article |
Chiral lipid bilayers are enantioselectively permeable
Droplet interface bilayer measurements have now shown that membranes formed from chiral phospholipid bilayers are enantioselectively permeable to chiral amino acids. The results show that membrane stereochemistry is necessary and sufficient to drive such enantioselective transport, presenting a new potential route to homochirality. These findings could also have implications for pharmacokinetics and drug design.
- Juan Hu
- , Wesley G. Cochrane
- & Brian M. Paegel
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Article |
A far-red hybrid voltage indicator enabled by bioorthogonal engineering of rhodopsin on live neurons
Voltage imaging is a powerful technique for studying electrical signalling in neurons. A palette of bright and sensitive voltage indicators has now been developed via enzyme-mediated ligation and Diels–Alder cycloaddition. Among these, a far-red indicator faithfully reports neuronal action potential dynamics with an excitation spectrum orthogonal to optogenetic actuators and green/red-emitting biosensors.
- Shuzhang Liu
- , Chang Lin
- & Peng Zou
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Article |
Expanding the antibacterial selectivity of polyether ionophore antibiotics through diversity-focused semisynthesis
Polyether ionophores are natural products that display antibacterial activity—but they also show activity against mammalian cells, which has limited their development as clinical antibiotics. Now, a semisynthesis principle of recycling substructures from highly abundant natural polyether ionophores has been used to prepare analogues with enhanced selectivity towards bacterial cells.
- Shaoquan Lin
- , Han Liu
- & Thomas B. Poulsen
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Article |
A fluorescent membrane tension probe
Lipid membranes—which separate cells and organelles from their environment—experience tension during various cell processes; however, measuring membrane tension is notoriously difficult. Now, a new fluorescent, mechanosensitive membrane probe called FliptR has been developed. FliptR enables simple, direct membrane tension measurements in cellular and artificial membranes.
- Adai Colom
- , Emmanuel Derivery
- & Aurélien Roux
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Article |
Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide
The trapping of antibodies in endosomes often limits their use for intracellular targeting. Now, a single amino acid substitution on a spider-venom peptide has been shown to attenuate the cell membrane lytic activity and enables the selective rupturing of endosomal membranes. The peptide can be used to facilitate the escape of antibodies from endosomes into the cytosol.
- Misao Akishiba
- , Toshihide Takeuchi
- & Shiroh Futaki
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Article |
Controlled membrane translocation provides a mechanism for signal transduction and amplification
The transmission of chemical information across lipid bilayer membranes is crucial in biological systems. Now, an artificial chemical system able to both transduce and amplify chemical signals across a membrane has been developed. The system works by exploiting the controlled translocation of a synthetic molecule that is embedded within a vesicle membrane.
- Matthew J. Langton
- , Flore Keymeulen
- & Christopher A. Hunter
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Article |
A monodisperse transmembrane α-helical peptide barrel
The assembly of transmembrane barrels formed from short synthetic peptides has not been previously demonstrated. Now, a transmembrane pore has been fabricated via the self-assembly of peptides. The 35-amino-acid α-helical peptides are based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza.
- Kozhinjampara R. Mahendran
- , Ai Niitsu
- & Hagan Bayley
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Article |
Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24
Off-target drug binding of anti-HIV protease inhibitors to a zinc metalloprotease has been suspected for some time. Now, mass spectrometry of human zinc metalloprotease ZMPSTE24 in the presence of four inhibitors has provided molecular evidence for this off-target binding. These results also enabled an investigation of the effects of the inhibitors on the processing of farnesylated prelamin A peptides.
- Shahid Mehmood
- , Julien Marcoux
- & Carol V. Robinson
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Article |
Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia
Synthetic anion transporters that replace the activity of defective anion channels have been proposed as treatments for cystic fibrosis; however, it remains uncertain whether such molecules are fundamentally toxic. A series of bis- and tris-(thio)ureas capable of transporting anions have now been tested in cells expressing halide-sensitive yellow fluorescent protein. One bis-urea compound proved especially effective while showing almost no toxicity.
- Hongyu Li
- , Hennie Valkenier
- & Anthony P. Davis
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Article |
A subset of annular lipids is linked to the flippase activity of an ABC transporter
Defining the lipid composition that exists around a membrane protein complex in natural bilayers is a challenging task. Now, key lipids that are important for the structure and function of an ABC transporter have been revealed by systematically removing layers of lipids, and using mass spectrometry to monitor those that remained closely associated with the membrane protein.
- Chérine Bechara
- , Anne Nöll
- & Carol V. Robinson
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Article |
Layer-by-layer cell membrane assembly
Immobilized microfluidic water-in-oil droplets serve as templates for layer-by-layer deposition of lipid monolayers to create vesicles of programmable lamellarity and content. Arrays of vesicles allow reproducible assembly and multi-vesicle probing of complex membrane-associated parameters, such as permeability, asymmetry and membrane protein function.
- Sandro Matosevic
- & Brian M. Paegel
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News & Views |
Gated access to microreactors
A pH-responsive inorganic membrane has been devised that acts as a gatekeeper for the transport of charged solutes into and out of its interior volume. This behaviour was further used to regulate an enzymatic reaction.
- Christine D. Keating
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News & Views |
Proton fronts on membranes
Proton migration on membranes is a crucial step in the bioenergetics of the cell. It has typically been regarded as slow successive proton transfers between ionizable moieties within the membrane, but recent measurements suggest fast lateral diffusion in the membrane's hydration layer.
- Noam Agmon
- & Menachem Gutman
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Research Highlights |
Peptides make the difference
Microporous crystals formed by hydrogen-bonded dipeptides show different permeabilities for argon, nitrogen and oxygen.
- Anne Pichon