Tunable Membrane Research Articles

A tuneable minimal cell membrane reveals that two lipid species suffice for life.

All cells are encapsulated by a lipid membrane which facilitates the interaction between life and its environment. How life exploits the diverse mixtures of lipids that dictate membrane property and function has been experimentally challenging to address. We introduce an approach to tune and minimize lipidomes in Mycoplasma mycoides and the Minimal Cell (JCVI-Syn3A) revealing that a 2-component lipidome can support life. Systematically reintroducing phospholipid features demonstrated that acyl chain diversity is more critical for growth than head group diversity. By tuning lipid chirality, we explored the lipid divide between Archaea and the rest of life, showing that ancestral lipidomes could have been heterochiral. Our approach offers a tunable minimal membrane system to explore the fundamental lipidomic requirements for life, thereby extending the concept of minimal life from the genome to the lipidome.

An In Vitro Model of the Blood-Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis.

The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L-lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi-porous membranes, these membranes significantly improve the expression of BBB-related proteins in brain endothelial cells. PEA-coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF-2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA-fibronectin membranes. This enables the generation of high-throughput drug permeability models without the need of complicated co-culture conditions.

An Integrated and Modular Compartmentalized Microfluidic System with Tunable Electrospun Porous Membranes for Epithelialized Organs-on-a-Chip.

A modular and 3D compartmentalized microfluidic system with electrospun porous membranes (PMs) for epithelialized organ-on-a-chip systems is presented. Our novel approach involves direct deposition of polymer nanofibers onto a patterned poly(methyl methacrylate) (PMMA) substrate using electrospinning, resulting in an integrated PM within the microfluidic chip. The in situ deposition of the PM eliminates the need for additional assembly processes. To demonstrate the high throughput membrane integration capability of our approach, we successfully deposited nanofibers onto various chip designs with complex microfluidic planar structures and expanded dimensions. We characterized and tested the fully PMMA chip by growing an epithelial monolayer using the Caco-2 cell line to study drug permeability. A comprehensive analysis of the bulk and surface properties of the membrane's fibers made of PMMA and polystyrene (PS) was conducted to determine the polymer with the best performance for cell culture and drug transport applications. The PMMA-based membrane, with a PMMA/PVP ratio of 5:1, allowed for the fabrication of a uniform membrane structure along the aligned nanofibers. By modulating the fiber diameter and total thickness of the membrane, we could adjust the membrane's porosity for specific cell culture applications. The PMMA-PVP nanofibers exhibited a low polydispersity index value, indicating monodispersed nanofibers and a more homogeneous and uniform fiber network. Both types of membranes demonstrated excellent mechanical integrity under medium perfusion flow rates. However, the PMMA-PVP composition offered a tailored porous structure with modulable porosity based on the fiber diameter and thickness. Our developed platform enables dynamic in vitro modeling of the epithelial barrier and has applications in drug transport and in vitro microphysiological systems.

Mid-Infrared Spectrometer Based on Tunable Photoresponses in Pdse2

Mid-infrared (mid-IR) photodetection is important for various applications, including biomedical diagnostics, security, chemical identification, and free-spacing optical communications. However, conventional “photon” mid-IR photodetectors require liquid nitrogen cooling (i.e., MCT). Furthermore, acquiring mid-IR spectra usually involves a complex and expensive Fourier Transform Infrared spectrometer, a tabletop instrument consisting of a meter-long interferometer and MCT detectors, which is not suitable for mobile and compact device applications. In this work, we present tunable photoresponsivity in the mid-IR wavelength in palladium diselenide (PdSe2) – molybdenum disulfide (MoS2) heterostructure field-effect transistors (FETs), operating at room temperature. Furthermore, we applied a tunable membrane cavity to modulate the Fabry–Pérot resonance to modulate the absorption spectrum of the device layer. We used a robust polyetherimide (PEI) membrane with CVD-grown graphene to electrically tune the membrane structure. For the next step, we will integrate the PdSe2-based photodetector and tunable membrane to increase detection sensitivity and spectrum tunability to realize the ‘learning’-based spectroscopy.

Ion-selective supramolecular membrane with pH-regulated smart nanochannels for lithium extraction

Tunable gating ion-conducting membranes with high water permeability and precise ion selectivity remain urgently demanded in smart nanofiltration for efficient lithium extraction. Herein, inspired by the filtration function of protein channels, we report a smart and high-performance supramolecular membrane constructed via coordination between quaternary ammonium ligands (m-phenylenediamine/polyethyleneimine) and metal ion center (Cu2+). The pore architecture of the supramolecular membrane is dynamic and can be switched by applying pH stimulus, where coordinated interchain expands when exposed to acidic operating conditions and induces concomitantly reinforced electrostatic exclusion due to enhanced local charge density. The tunable gating regularity enables operando modulation of precise ionic separation in situ. The resulting membrane exhibits significantly enhanced water permeance (19.8 L m−2 h−1·bar−1) and simultaneously promoted Li+/Mg2+ selectivity (RMg2+ = 96.4 %), surpassing typical trade-off between permeability and selectivity at pH 3 condition. This study demonstrates the amazing capability of environmental-responsive regulation of membrane pore-channel structure, and provides inspiration for engineering advanced supramolecular membranes for lithium extraction and beyond.

Tuning the interlayer spacing of graphene oxide membrane via surfactant intercalation for ultrafast nanofiltration

A facile method has been developed to fabricate lamellar composite graphene oxide (CGO) membranes by incorporating positively charged surfactants – cetyltrimethylammonium bromide (CTAB). The interlayer spacing of GO nanosheets was regulated by the sum of both vertical and horizontal alignment of CTAB on the GO surface via electrostatic interaction. The CTAB intercalated GO membrane exhibited an internal layer spacing of 16.97 Å compared to 8.26 Å for the GO membrane. The obtained CGO lamellar membrane with well-defined nanochannels showed ultrafast pure water flux of ∼1112 L h−1 m−2 bar−1 and an excellent separation efficiency of >99 % towards negatively charged organic dye molecules at a high permeation flux of ∼932 L h−1 m−2 bar−1, which was nearly 2.5-fold enhancement compared with that of the pristine GO membrane (∼400 L h−1 m−2 bar−1). The electrostatic and π–π interaction forces between the CGO membrane and organic dye molecules played a major role in the overall dye separation mechanism. Furthermore, the CGO membrane demonstrated excellent stability with no loss in separation performance (>96 % organic molecules rejection) after exposure to various pH solutions and deionized water (DI) water. The current work provides a straightforward approach for the formation of highly tunable and stable CTAB-intercalated GO membranes for ultrafast molecular separation.

Highly Stretchable Polyurethane Porous Membranes with Adjustable Morphology for Advanced Lithium Metal Batteries.

A highly flexible, tunable morphology membrane with excellent thermal stability and ionic conductivity can endow lithium metal batteries with high power density and reduced dendrite growth. Herein, a porous Polyurethane (PU) membrane with an adjustable morphology was prepared by a simple nonsolvent-induced phase separation technique. The precise control of the final morphology of PU membranes can be achieved through appropriate selection of a nonsolvent, resulting a range of pore structures that vary from finger-like voids to sponge-like pores. The implementation of combinatorial DFT and experimental analysis has revealed that spongy PU porous membranes, especially PU-EtOH, show superior electrolyte wettability (472%), high porosity (75%), good mechanical flexibility, robust thermal dimensional stability (above 170 °C), and elevated ionic conductivity (1.38 mS cm-1) in comparison to the polypropylene (PP) separator. The use of PU-EtOH in Li//Li symmetric cell results in a prolonged lifespan of 800 h, surpasing the longevity of PU or PP cells. Moreover, when subjected to a high rate of 5 C, the LiFePO4/Li half-cell with a PU-EtOH porous membrane displayed better cycling performance (115.4 mAh g-1) compared to the PP separator (104.4 mAh g-1). Finally, the prepared PU porous membrane exhibits significant potential for improving the efficiency and safety of LMBs.

From cell membrane to endoplasmic reticulum: Tunable lipid membrane imaging by regulating the lipophilicity and internalization of carbon dots

The interactions between various organelles play a crucial role on cellular activity, and the design and construction of multi-organelle fluorescent probes is of great challenges. Herein, fluorescent CDs with tunable cell plasma membrane and lipid-rich organelle-targeting ability were fabricated via exquisitely regulating the ratio of tridecanedioic acid and m-diethylaminophenol as the co-precursor, combining the structure–activity relationship to modulate the CDs structure and surficial property. Condensation of m-diethylaminophenol in the presence of different amount of tridecanedioic acid was exploited to construct MCDs and ECDs for targeted cell membrane and endoplasmic reticulum imaging respectively. The appropriately incorporated alkyl chains as membrane anchoring group and the suppressed internalization by carboxyl group led to the retention of MCDs in cell membrane, while the excessive introduction of alkyl chains offered ECDs with high lipophilicity, resulting in the rapid internalization and subsequential distribution in endoplasmic reticulum membrane. The favorable membrane retention capability and excellent photostability make MCDs an excellent probe for long-term targeted-imaging of cell membrane in vitro, with remarkable tracking duration long to five passages and effectively display cell membrane morphological dynamics during cell division and cell death. Moreover, real-time evaluation of cholesterol consumption of Lo phase in cell membrane via ratiometric fluorescence imaging was achieved, attributed to the sensitive response of CDs to polarity variations.

Practical organic electronic noses using semi-permeable polymer membranes

Electronic noses (E-noses) mimic olfactory organs and quantify volatile organic compounds (VOCs), emulating the sense of smell, with applications in real-time monitoring of VOCs in food, healthcare, and law enforcement industries. Organic field-effect transistor (OFET) based sensors can be fabricated in large arrays by economical processes, however, lack the selectivity necessary to differentiate wide varieties of VOCs. Here, we explore the use of permeable polymer membranes with OFET sensors to improve their selectivity. Acylated poly(vinyl alcohol) (PVA) derivatives were synthesized, characterized, and evaluated in OFET vapor sensors as tunable membranes. Sensors with and without acylated PVA membranes were tested with VOC analytes. By monitoring drain current over time, we found that membranes dramatically changed responses to different analytes. We show that VOCs including methanol, ethanol, hexane, toluene, tetrahydrofuran, methyl ethyl ketone, and ethyl acetate can all be detected and differentiated with much greater selectivity than sensors without membranes. In particular, methanol and ethanol, which are difficult to differentiate in vapor sensors, showed significant quantitative differences in the initial slope (0.0403 s−1 vs 0.0192 s−1 respectively; 6 σ) and decay constants (5.5 s vs 15.9 s respectively; 26 σ) of their current vs time responses, allowing methanol and ethanol to be differentiated with 100 % confidence. This approach enables the economical fabrication of large varieties of unique organic vapor sensors by simply changing the membrane layer and results in an outstanding level of selectivity for OFET vapor sensors.

Determining the membrane recruitment mechanisms of peripheral membrane proteins through native mass spectrometry directly from tunable lipid membranes

Determining the membrane recruitment mechanisms of peripheral membrane proteins through native mass spectrometry directly from tunable lipid membranes

Fabrication of Breathable Multifunctional On-Skin Electronics Based on Tunable Track-Etched Membranes

Fabrication of Breathable Multifunctional On-Skin Electronics Based on Tunable Track-Etched Membranes

High-Temporal-Resolution In Situ Sensor for Oceanic CO2 Isotope Measurement Enabling Multidimensional Isotope Tracing Analysis (R13C, R18O, and R17O) via Laser Absorption Spectroscopy.

Combined in situ analysis of oceanic CO2 concentrations and diverse C and O isotope characteristics can offer a unique perspective with multiple isotopic tracing dimensions for identifying marine biogeochemical processes. Applying this strategy in marine environments is urgently required, yet it faces inherent challenges in terms of existing analytical methods and instruments, e.g., a lack of in situ sensors, limited detectable isotope variety, and low-temporal-resolution data. Here, we report an underwater in situ dissolved CO2 isotope sensor based on mid-infrared tunable diode laser absorption spectroscopy (MIR-TDLAS) and membrane extraction technology. Through the proposed targeted strategies, the sensor is capable of providing high-temporal-resolution in situ measurement of all monosubstituted isotopes of dissolved CO2 (16O13C16O, 18O12C16O, and 17O12C16O) at marine background concentrations. The sensor is demonstrated to provide comparable precision to that of isotope ratio mass spectrometry. At 400 ppmv, the precision for R13C, R18O, and R17O could achieve 0.084, 0.042, and 0.013‰, respectively, for a 1 s integration time. By enabling a high-frequency in situ analysis in fixed-point time-series field deployment, a 17O anomaly with strong regularity is observed, which is not obvious in 18O and 13C, and therefore, the superiority of the proposed multidimensional in situ isotope tracing strategy is demonstrated. The developed sensor has great potential to open up new prospects for advancing marine carbon research.

A novel tunable polypropylene hollow fiber membrane with gradient structure for extracorporeal membrane oxygenation applications

High gas permeability and excellent resistance to plasma leakage are expected from polypropylene (PP) hollow fiber membranes (HFMs) used in extracorporeal membrane oxygenation (ECMO) systems. This study successfully prepared a novel PP HFMs with tunable and gradient structures using oleic acid (OA) and methyl-5-(dimethylamino)-2-methyl-5-oxopentanoate (RhodiasolvⓇ PolarClean) (PL) as binary diluents via the hybrid induced phase separation (HIPS) method. The phase-separation behavior of the PP-OA/PL system was studied using a phase diagram and the resultant membrane structure. As the concentration of PL in the binary diluents increased, the phase separation mechanism changed from solid–liquid (S–L) to liquid–liquid (L–L), and the structure of PP HFMs changed from crystalline to cellular or bi-continuous. Moreover, the effects of PP concentration and air gap distance on the membrane structure and performance were investigated. In particular, the obtained HFMs showed a clear gradient configuration. The results showed that when the PP concentration, OA to PL mass ratio, and air gap were set to 35 wt%, 7/3, and 10 mm, respectively, the PP HFM exhibited the optimal performance with a high N2 permeability of 23.42 ± 0.98 ml/(min cm2 bar) and resistance to simulated plasma leakage of 4300 min.

A new class of “structure-by-design” polymer membranes for organic solvent nanofiltration with controllable selectivity

Membrane based separations offer an inexpensive and energy efficient pathway to purification. However, their use is often stifled during separation of organics due to low selectivity. This can be attributed to the inherent limitations of the synthesis methods employed, namely, interfacial polymerization and phase inversion. In this work, a new class of structure-by-design membranes are synthesized by surface modification of crosslinked polyimide using graft polymerization with a series of methacrylate monomers with differing chain lengths and chemistries. Graft polymerization of long chain monomers resulted in increased selectivity (α∼3.7 for 80-20 mol.% MeOH-toluene and α∼6 for 95-5 mol.% toluene-triisopropyl benzene (TIPB) for both test solutions) as a result of increased stiffness and order (using GIWAXS)). The observed selectivities renders these membranes competitive for organic solvent nanofiltration applications. In addition, pure solvent permeabilities were measured. The performance of these membranes was correlated with brush properties such as degree of grafting (using ATR-FTIR), surface polarity (contact angle measurements), stiffness (using QCM-D) and brush configuration in different solvent environments (using MD Simulations). MD simulations demonstrate that in mixtures containing hydrophobic species, polymers with longer hydrophobic side chains well more and form fuller matrices leading to increased solvent accessible surface area. GIWAXS results showed increased order with longer side chain length. These tunable membranes offer promise for organics separation.

Amphiphilic Polyampholytes for Fouling-Resistant and Easily Tunable Membranes.

The versatility of membranes is limited by the narrow range of material chemistries on the market, which cannot address many relevant separations. Expanding their use requires new membrane materials that can be tuned to address separations by providing the desired selectivity and robustness. Self-assembly is a versatile and scalable approach to create tunable membranes with a narrow pore size distribution. This study reports the first examples of a new class of membrane materials that derives state-of-the-art permeability, selectivity, and fouling resistance from the self-assembly of random polyampholyte amphiphilic copolymers. These membranes feature a network of ionic nanodomains that serve as nanochannels for water permeation, framed by hydrophobic nanodomains that preserve their structural integrity. This copolymer design approach enables precise selectivity control. For example, sodium sulfate rejections can be tuned from 5% to 93% with no significant change in the pore size or fouling resistance. Membranes developed here have potential applications in wastewater treatment and chemical separations.

Do Nanodisc Assembly Conditions Affect Natural Lipid Uptake?

Lipids play critical roles in modulating membrane protein structure, interactions, and activity. Nanodiscs provide a tunable membrane mimetic that can model these endogenous protein-lipid interactions in a nanoscale lipid bilayer. However, most studies of membrane proteins with nanodiscs use simple synthetic lipids that lack the headgroup and fatty acyl diversity of natural extracts. Prior research has successfully used natural lipid extracts in nanodiscs that more accurately mimic natural environments, but it is not clear how nanodisc assembly may bias the incorporated lipid profiles. Here, we applied lipidomics to investigate how nanodisc assembly conditions affect the profile of natural lipids in nanodiscs. Specifically, we tested the effects of assembly temperature, nanodisc size, and lipidome extract complexity. Globally, our analysis demonstrates that the lipids profiles are largely unaffected by nanodisc assembly conditions. However, a few notable changes emerged within individual lipids and lipid classes, such as a differential incorporation of cardiolipin and phosphatidylglycerol lipids from the E. coli polar lipid extract at different temperatures. Conversely, some classes of brain lipids were affected by nanodisc size at higher temperatures. Collectively, these data enable the application of nanodiscs to study protein-lipid interactions in complex lipid environments.

Cellulose acetate-based smart gating membrane with pH/thermal response for flux control

Inspired by the stomatal opening and closing mechanism of plants, a cellulose acetate-based pH/thermal response smart gating membrane was designed through surface segregation mechanism by embedding stimulation-responsive poly(N- isopropylacrylaminde) (PNIPAM)/poly(acrylic acid) (PAAc) microgels in the membrane pore channels. The water flux of the optimized smart membrane (CAM1.5) is 0.420 L/m2·h at 20 ℃/pH= 11 and changes to 121 L/m2·h at 65 ℃/pH= 1 with the highest gating ratio of 174. Meanwhile, the membrane gating ratio can be further improved to 216 when citric acid is used as coagulation bath. The carboxyl group content in the PAAc side chain is decreased and the interaction between water and microgels is improved under acid environment, which promotes the surface segregation of microgel. In addition, there is significant increase in the wet strength owing to the covalent crosslinking of citric acid. A fluid control system was designed based on the tunable membrane pore structure. According to the change of temperature and pH of the reaction system, the membrane can be opened and closed independently to precisely control the flow of reactants. This smart membrane shows promising applications in micro/nano fluid valves and temperature/pH sensitive biochemical reactors.

Studying Membrane Protein-Lipid Specificity through Direct Native Mass Spectrometric Analysis from Tunable Proteoliposomes.

Native mass spectrometry (nMS) has emerged as a key analytical tool to study the organizational states of proteins and their complexes with both endogenous and exogenous ligands. Specifically, for membrane proteins, it provides a key analytical dimension to determine the identity of bound lipids and to decipher their effects on the observed structural assembly. We recently developed an approach to study membrane proteins directly from intact and tunable lipid membranes where both the biophysical properties of the membrane and its lipid compositions can be customized. Extending this, we use our liposome-nMS platform to decipher the lipid specificity of membrane proteins through their multiorganelle trafficking pathways. To demonstrate this, we used VAMP2 and reconstituted it in the endoplasmic reticulum (ER), Golgi, synaptic vesicle (SV), and plasma membrane (PM) mimicking liposomes. By directly studying VAMP2 from these customized liposomes, we show how the same transmembrane protein can bind to different sets of lipids in different organellar-mimicking membranes. Considering that the cellular trafficking pathway of most eukaryotic integral membrane proteins involves residence in multiple organellar membranes, this study highlights how the lipid-specificity of the same integral membrane protein may change depending on the membrane context. Further, leveraging the capability of the platform to study membrane proteins from liposomes with curated biophysical properties, we show how we can disentangle chemical versus biophysical properties, of individual lipids in regulating membrane protein assembly.

Tunable biomimetic bacterial membranes from binary and ternary lipid mixtures and their application in antimicrobial testing

The reconstruction of accurate yet simplified mimetic models of cell membranes is a very challenging goal of synthetic biology. To date, most of the research focuses on the development of eukaryotic cell membranes, while reconstitution of their prokaryotic counterparts has not been fully addressed, and the proposed models do not reflect well the complexity of bacterial cell envelopes. Here, we describe the reconstitution of biomimetic bacterial membranes with an increasing level of complexity, developed from binary and ternary lipid mixtures. Giant unilamellar vesicles composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); PC and phosphatidylglycerol (PG); PE and PG; PE, PG and cardiolipin (CA) at varying molar ratios were successfully prepared by the electroformation method. Each of the proposed mimetic models focuses on reproducing specific membrane features such as membrane charge, curvature, leaflets asymmetry, or the presence of phase separation. GUVs were characterized in terms of size distribution, surface charge, and lateral organization. Finally, the developed models were tested against the lipopeptide antibiotic daptomycin. The obtained results showed a clear dependency of daptomycin binding efficiency on the amount of negatively charged lipid species present in the membrane. We anticipate that the models proposed here can be applied not only in antimicrobial testing but also serve as platforms for studying fundamental biological processes in bacteria as well as their interaction with physiologically relevant biomolecules.

Temperature-Responsive Nanoporous Membranes from Self-Assembly of Poly(N-isopropylacrylamide) Hairy Nanoparticles.

Nanoporous membranes play a critical role in numerous separations on laboratory and industrial scales, ranging from water treatment to biotechnology. However, few strategies exist that allow for the preparation of mechanically robust nanoporous membranes whose separation properties can be easily tuned. Here, we introduce a new family of tunable nanoporous membranes based on nanoparticles decorated with temperature-responsive polymer brushes. We prepared mechanically robust membranes from hairy nanoparticles (HNPs) carrying PNIPAM polymer brushes. We assembled the HNPs into thin films through pressure-driven deposition of nanoparticle suspensions and measured the permeability and filtration cutoff of these membranes at different temperatures. The membrane pore diameter at room temperature varied between 10 and 30 nm depending on the polymer length. The water permeability of these membranes could be controlled by temperature, with the effective pore diameter increasing by a factor of 3-6 (up to 100 nm) when the temperature was increased to 60 °C. The size selectivity of these membranes in the filtration of nanoparticles could also be attenuated by temperature. Molecular dynamics computer simulations of a coarse-grained HNP model show that temperature-sensitive pores sizes are consistent with our experimental results and reveal the polymer configurations responsible for the observed filtration membrane permeability. We expect that these membranes will be useful for separations and in the preparation of responsive microfluidic devices.