A5060538791- Lipid Membrane Structure and Behavior
- Nanopore and Nanochannel Transport Studies
- Ion channel regulation and function
- Force Microscopy Techniques and Applications
- Erythrocyte Function and Pathophysiology
- Advanced biosensing and bioanalysis techniques
- Protein Structure and Dynamics
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- Photochromic and Fluorescence Chemistry
- Mass Spectrometry Techniques and Applications
- Microfluidic and Capillary Electrophoresis Applications
- Ion-surface interactions and analysis
- Polymer Surface Interaction Studies
- Photoreceptor and optogenetics research
- Nanoparticle-Based Drug Delivery
- Mechanical and Optical Resonators
- Biochemical and Structural Characterization
- Biochemical Analysis and Sensing Techniques
- Electron Spin Resonance Studies
- Protein Degradation and Inhibitors
- Hemoglobin structure and function
- Heat shock proteins research
- Cardiomyopathy and Myosin Studies
- Biosensors and Analytical Detection
University of Twente
2008-2023
University of Groningen
2005-2017
University Medical Center Groningen
2014-2017
Instituto de Investigaciones Biomédicas Sols-Morreale
2017
Universidad Autónoma de Madrid
2017
Institute of Molecular Life Sciences
2012-2014
Université de Montpellier
2012
Centre National de la Recherche Scientifique
2012
Institut Charles Gerhardt Montpellier
2012
Institut Européen des Membranes
2012
Toward the realization of nanoscale device control, we report a molecular valve embedded in membrane that can be opened by illumination with long-wavelength ultraviolet (366 nanometers) light and then resealed visible irradiation. The consists channel protein, mechanosensitive large conductance (MscL) from Escherichia coli, modified attachment synthetic compounds undergo light-induced charge separation to reversibly open close 3-nanometer pore. system is compatible classical encapsulation...
A wide variety of phytochemicals are consumed for their perceived health benefits. Many these have been found to alter numerous cell functions, but the mechanisms underlying biological activity tend be poorly understood. Phenolic particularly promiscuous modifiers membrane protein function, suggesting that some actions may due a common, bilayer-mediated mechanism. To test whether bilayer perturbation underlie this diversity actions, we examined five bioactive phenols reported medicinal...
Significance Understanding the working mechanism of membrane proteins is difficult even when crystal structures are available. One promising approach ion mobility–mass spectrometry (IM-MS) that detects not only mass-to-charge ratio but also area by measuring rotationally averaged collision cross-sections (CCS) in gas phase. We identified detergents allow release at low levels collisional activation for native MS, thus avoiding denaturing effects. studied gating an channel, which occurs...
The mechanism of action antimicrobial peptides is, to our knowledge, still poorly understood. To probe the biophysical characteristics that confer activity, we present here a molecular-dynamics and study cyclic peptide its inactive linear analog. In simulations, caused large perturbations in bilayer cooperatively opened disordered toroidal pore, 1–2 nm diameter. Electrophysiology measurements confirm discrete poration events comparable size. We also show lysine residues aligning parallel...
Mechanosensitive (MS) ion channels are membrane proteins that detect and respond to tension in all branches of life. In bacteria, MS prevent cells from lysing upon sudden hypoosmotic shock by opening releasing solutes water. Despite the importance ongoing efforts explain their functioning, molecular mechanism channel gating remains elusive controversial. Here we report a method allows single-subunit resolution for manipulating monitoring “mechanosensitive large conductance” Escherichia coli...
The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case severe osmotic downshock. Sensing bilayer tension, MscL sensitive to changes the environment and are, therefore, an ideal test for exploring protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations characterize gating kinetics different environments under influence alcohols. We performed over five hundred...
Open channels: Chemical modulators are developed to convert a naturally occurring channel protein into pH-actuated nanovalve. The pH interval, sensitivity, and activation of the valve by opening tunable through design modulators. is useful for releasing or mixing contents liposomes at desired location, time, dosage, example, in micro/nanosensory delivery devices (see picture). Supporting information this article available on WWW under...
One of the best-studied mechanosensitive channels is channel large conductance (MscL). MscL senses tension in membrane evoked by an osmotic down shock and directly couples it to conformational changes leading opening channel. Spectroscopic techniques offer unique possibilities monitor these if were possible generate lipid bilayer, native environment MscL, during measurements. To this end, asymmetric insertion L-α-lysophosphatidylcholine (LPC) into bilayer has been effective; however, how LPC...
Abstract Here we study the intact stoichiometry and top‐down fragmentation behavior of three integral membrane proteins which were natively reconstituted into detergent micelles: mechano‐sensitive ion channel large conductance (MscL), Kirbac potassium p7 viroporin from hepatitis C virus. By releasing under nondenaturing conditions inside mass spectrometer, obtained their oligomeric sizes. Increasing activation (collision energy) causes unfolding subsequent ejection a highly charged monomer...
Abstract To mimic the selectivity and properties of biological channels pumps, adaptive systems can be designed using artificial membranes. One big advantage those membranes is that they are able to respond several stimuli at same time. Here, it proposed tailor conical nanopores by grafting polyethyleneglycol (PEG)‐spiropyrans in order combine both light‐ pH‐responsive properties. The study ionic transport reveals after UV irradiation nanopore open while visible irradiation, closed. This...
Membrane proteins are prime drug targets as they control the transit of information, ions, and solutes across membranes. Here, we present a membrane-on-nanopore platform to analyze nonelectrogenic channels transporters that typically not accessible by electrophysiological methods in multiplexed manner. The silicon chip contains 250,000 femtoliter cavities, closed dioxide top layer with defined nanopores. Lipid vesicles containing membrane interest spread onto nanopore-chip surface. Transport...
Myosin II propelled actin filaments move ten times faster than kinesin driven microtubules and are thus attractive candidates as cargo-transporting shuttles in motor lab-on-a-chip devices. In addition, actomyosin-based transportation of nanoparticles is useful various fundamental studies. However, it poorly understood how actomyosin function affected by different number nanoscale cargoes, cargo size, the mode cargo-attachment to filament. This studied here using biotin/fluorophores,...
Elucidation of high-resolution structures integral membrane proteins is drastically lagging behind that cytoplasmic proteins. In vitro synthesis and insertion into synthetic membranes could circumvent bottlenecks associated with the overexpression proteins, producing sufficient membrane-inserted, correctly folded protein for structural studies. Using mechanosensitive channel large conductance, MscL, as a model we show in synthesized MscL inserts YidC-containing proteoliposomes oligomerizes...
The mechanosensitive channel of large conductance (MscL) is a homopentameric membrane protein that protects bacteria from hypoosmotic stress. Its mechanics are coupled to structural changes in the membrane, yet molecular mechanism transition closed open states and cooperation between subunits poorly understood. To determine early stages activation, we have created chemically addressable heteropentameric MscL, which allows us selectively trigger only one subunit pentameric assembly. By...
Single molecule studies on membrane proteins embedded in their native environment are hampered by the intrinsic difficulty of immobilizing elastic and sensitive biological membranes without interfering with protein activity. Here, we present hydrogels composed nano-scaled fibers as a generally applicable tool to immobilize vesicles various size lipid composition. Importantly, immobilized hydrogel well soluble fully active. The triggered opening mechanosensitive channel large conductance...
In order to reduce the toxicity and increase efficacy of drugs, there is a need for smart drug delivery systems. Liposomes are one promising tools this purpose. An ideal liposomal system should be stable, long-circulating, accumulate at target site release its in controlled manner. Even though have been many developments end, dilemma having stable liposome during circulation but converting it into leaky structure still major challenge. So far, most attempts focused on destabilizing response...
We have successfully developed, for the first time, a novel polymer–lipid hybrid nanocontainer with controlled permeability functionality. The is made by nanofabricating holes desired dimensions in an impermeable polymer scaffold focused ion beam drilling and sealing them lipid bilayers containing remote-controlled pore-forming channel proteins. This system allows exchange of solutions only after activation at will to form temporary pores container. Potential applications are foreseen...
Kanal öffne dich! Chemische Modulatoren verwandeln ein natürliches Kanalprotein in pH-gesteuertes Nanoventil. Der pH-Bereich, die Empfindlichkeit und Aktivierung des Ventils durch Öffnen Kanals lassen sich gezielt beeinflussen. Derartige Ventile könnten den Inhalt von Liposomen zeit- dosierungsgenau an einem Zielort freisetzen, etwa Mikro- oder Nano-Sensoren -Transportern (siehe Bild).