Membrane Mechanical Properties Research Articles

Label-Free Quantification of Molecular Interaction in Live Red Blood Cells by Tracking Nanometer Scale Membrane Fluctuations.

Molecular interactions in live cells play an important role in both cellular functions and drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, while the in situ quantification of molecular interaction with surface plasmon resonance (SPR) imaging mainly worked with fixed cells due to the micro-motion related noises of live cells. Here, an optical imaging method is presented to measure the molecular interaction with live red blood cells by tracking the nanometer membrane fluctuations. The membrane fluctuation dynamics are measured by tracking the membrane displacement during glycoprotein interaction. The data are analyzed with a thermodynamic model to determine the elastic properties of the cell observing reduced membrane fluctuations under fixatives, indicating cell fixations affect membrane mechanical properties. The binding kinetics of glycoprotein to several lectins are obtainedby tracking the membrane fluctuation amplitude changes on single live cells. The binding kinetics and strength of different lectins are quite different, indicating the glycoproteins expression heterogeneity in single cells. It is anticipated that the method will contribute to the understanding of mechanisms of cell interaction and communication, and have potential applications in the mechanical assessment of cancer or other diseases at the single-cell level, and screening of membrane protein targeting drugs.

Lipidomic and Membrane Mechanical Signatures in Triple-Negative Breast Cancer: Scope for Membrane-Based Theranostics.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer associated with poor prognosis, higher grade, and a high rate of metastatic occurrence. Limited therapeutic interventions and the compounding issue of drug resistance in triple-negative breast cancer warrants the discovery of novel therapeutic targets and diagnostic modules. To this view, in addition to proteins, lipids also regulate cellular functions via the formation of membranes that modulate membrane protein function, diffusion, and their localization; thus, orchestrating signaling hot spots enriched in specific lipids/proteins on cell membranes. Lipid deregulation in cancer leads to reprogramming of the membrane dynamics and functions impacting cell proliferation, metabolism, and metastasis, providing exciting starting points for developing lipid-based approaches for treating TNBC. In this review, we provide a detailed account of specific lipidic changes in breast cancer, link the altered lipidome with membrane structure and mechanical properties, and describe how these are linked to subsequent downstream functions implicit in cancer progression, metastasis, and chemoresistance. At the fundamental level, we discuss how the lipid-centric findings in TNBC are providing cues for developing lipid-inspired theranostic strategies while bridging existing gaps in our understanding of the functional involvement of lipid membranes in cancer.

Distinct contributions of ECM proteins to basement membrane mechanical properties in Drosophila.

The basement membrane is a specialized extracellular matrix (ECM) that is crucial for the development of epithelial tissues and organs. In Drosophila, the mechanical properties of the basement membrane play an important role in the proper elongation of the developing egg chamber; however, the molecular mechanisms contributing to basement membrane mechanical properties are not fully understood. Here, we systematically analyze the contributions of individual ECM components towards the molecular composition and mechanical properties of the basement membrane underlying the follicle epithelium of Drosophila egg chambers. We find that the Laminin and Collagen IV networks largely persist in the absence of the other components. Moreover, we show that Perlecan and Collagen IV, but not Laminin or Nidogen, contribute greatly towards egg chamber elongation. Similarly, Perlecan and Collagen, but not Laminin or Nidogen, contribute towards the resistance of egg chambers against osmotic stress. Finally, using atomic force microscopy we show that basement membrane stiffness mainly depends on Collagen IV. Our analysis reveals how single ECM components contribute to the mechanical properties of the basement membrane controlling tissue and organ shape.

Polypropylene Hollow Fiber Membrane by Dissolution-Inducing Pore Methods.

Plasma leakage limits the development of polypropylene membranes as oxygenated membranes. Here, a new method named the dissolution-induced pore method was adapted to prepare polypropylene hollow fiber membranes: after polypropylene and polyvinyl chloride were melt-blended and extruded, the polyvinyl chloride was removed by N, N-dimethylacetamide to obtain a porous polypropylene membrane material. The variation of membranes has been explored in detail with respect to the influence of different parameters on the flux and mechanical properties of membranes and the feasibility of the polyvinyl chloride recovery. The resulting polypropylene hollow fiber membrane shows that plasma penetration was zero within 6 h of test, gas flux can reach 189,000 L/(m2·h·0.1 MPa), and its strength at break reaches 65 MPa and the elongation at break is 890%; polyvinyl chloride recovery achieves more than 99%. This research has developed a promising and low-cost extracorporeal membrane oxygenation material, which provides benefits for patients with less capacity for medical expenditure.

Achieving high power density of 859.5 mW cm−2: Self-cross-linking polymer membrane based on rigid fluorenone structure

Plasticization of phosphoric acid (PA) leads to deterioration of the mechanical properties of polybenzimidazole membranes. It has been widely accepted that cross-linking is an effective method to improve mechanical properties of membranes. However, cross-linked membranes generally exhibit decreased proton conductivity and poor fuel cell performance. In this work, a self-cross-linking copolymer based on rigid fluorenone-modified polybenzimidazole (FPBI) are designed and synthesized as high-temperature proton exchange membranes for the first time. The cross-linked FPBI membranes are prepared through solvent casting and the cross-linking degrees of the membranes can be controlled by adjusting membrane preparation temperature and evaporation speed of the solvent. The membranes exhibit excellent mechanical properties and high proton conductivities. The membrane with FPBI-80 °C exhibits high oxidation resistance (>80 wt%), PA retention property (>90 wt%), tensile strength (12.08 MPa), and elongation at break (212.7%). The single cell based on FPBI-80 °C exhibits a high open-circuit voltage (1.01 V) and excellent peak power density of 859.5 mW cm−2 at 160 °C in an anhydrous environment. Herein, the FPBI membrane is expected to be applied in high-temperature fuel cells.

Serotonergic drugs modulate the phase behavior of complex lipid bilayers

Serotonin is an endogenous neurotransmitter involved in both physiological and pathophysiological processes. Traditionally, serotonin acts as a ligand for G protein-coupled receptors (GPCRs) leading to subsequent cell signaling. However, serotonin can also bind to lipid membranes with high affinity and modulate the phase behavior in 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC)/N-palmitoyl-D-erythro-sphingosylphosphorylcholine (PSM)/cholesterol model membranes mimicking the outer leaflet of the plasma membrane. Here, we investigated if serotonergic drugs containing the pharmacophore from serotonin would also modulate phase behavior in lipid membranes in a similar fashion. We used 2H NMR spectroscopy to explore the phase behavior of POPC/PSM/cholesterol (4/4/2 molar ratio) mixtures in the presence of the serotonergic drugs aripiprazole, BRL-54443, BW-723C86, and CP-135807 at a lipid to drug molar ratio of 10:1. POPC and PSM were perdeuterated in the palmitoyl chain, respectively, and prepared in individual samples. Numerical lineshape simulations of the 2H NMR spectra were used to calculate the order parameter profiles and projected lengths of the saturated acyl chains. All serotonergic drugs induce two components in 2H NMR spectra, indicating that they increased the hydrophobic mismatch between the thickness of the coexisting lipid phases leading to larger domain sizes, relatively similarly to serotonin. AFM force indentation and Raman spectral studies, which interrogate membrane mechanical properties, also indicate changes in membrane order in the presence of these drugs. These findings highlight how serotonergic drugs alter membrane phase behavior and could modulate both target and other membrane proteins, possibly explaining the side effects observed for serotonergic and other clinically relevant drugs.

Morphological Characteristics, Hemoglobin Content, and Membrane Mechanical Properties of Red Blood Cell Delivery Systems.

Red blood cell (RBC)-based systems are under extensive development as platforms for the delivery of various biomedical agents. While the importance of the membrane biochemical characteristics in relation to circulation kinetics of RBC delivery systems has been recognized, the membrane mechanical properties of such carriers have not been extensively studied. Using optical methods in conjunction with image analysis and mechanical modeling, we have quantified the morphological and membrane mechanical characteristics of RBC-derived microparticles containing the near-infrared cargo indocyanine green (ICG). We find that these particles have a significantly lower surface area, volume, and deformability as compared to normal RBCs. The residual hemoglobin has a spatially distorted distribution in the particles. The membrane bending modulus of the particles is about twofold higher as compared to normal RBCs and exhibits greater resistance to flow. The induced increase in the viscous characteristics of the membrane is dominant over the elastic and entropic effects of ICG. Our results suggest that changes to the membrane mechanical properties are a result of impaired membrane-cytoskeleton attachment in these particles. We provide a mechanistic explanation to suggest that the compromised membrane-cytoskeleton attachment and altered membrane compositional and structural asymmetry induce curvature changes to the membrane, resulting in mechanical remodeling of the membrane. These findings highlight the importance of membrane mechanical properties as an important criterion in the design and engineering of future generations of RBC-based delivery systems to achieve prolonged circulation.

Fabrication of high flux porphrin-cored with siloxane-poly(amido amine) dendrimer/PVDF composite membrane for oil/water separation and dye degradation

The effective separation of oil-water emulsion and the degradation of organic dyes are significant for solving the problem of environmental pollution. In this view, porphrin-cored with siloxane-poly(amido amine) dendrimer(PP-Si-PAMAM) blending PVDF composite membrane (PP-Si-PAMAM/PVDF) was successfully prepared by using simple non-solvent-induced phase inversion method. After introducing PP-Si-PAMAM into PVDF membrane matrix, the porosity, hydrophilicity and mechanical properties of the composite membrane were significantly improved. The resultant membrane exhibits admirable separation performance (above 99.1%) and high permeation flux (830–1471 L∙m−2∙h−1∙bar−1) for a series of oil-water emulsions. After 10 cycles of separation, the separation efficiency of the PP-Si-PAMAM/PVDF membrane is still more than 99%, and it still maintains excellent separation efficiency and permeability after extreme chemical environment treatment. Moreover, PP-Si-PAMAM/PVDF membrane has excellent degradation effect on organic dyes RhB and MB under visible light, and the degradation efficiency reaches 88% and 90% respectively in a short time. This work has huge potential applications in wastewater treatment with its combined advantages of oil-water emulsion separation and catalytic degradation of organic dye contaminants.

Study of the Effect of Hydrolysis Time on the Mechanical Properties of Polysiloxane Microcapsules

It is known that the microstructure and thereby the mechanical properties of membranes constituting microcapsules are sensitive to parameters such as precursor concentration and pH. In the case of polysiloxane microcapsules, the oligomers, which are already formed in the continuous oil phase, because of the inherent moisture content in the oil phase, deposit on the membrane surface, resulting in the formation of a microstructure with a hairy layer. An electrodeformation investigation shows that the deposition of these oligomers is predominant in the smaller microcapsules compared to the larger ones and results in strain hardening and plasticity in the microcapsule membrane at high deformation. However, if the hydrolysis time during the synthesis of microcapsules is controlled, a smooth morphology (with a diminished hairy layer) can be realized for smaller capsules, as well. This work, using the electrodeformation method, demonstrates significant viscoelasticity and plasticity in the response of the capsules to applied electric stress and establishes an equivalence between simple spring and dashpot element-based phenomenological models with respect to the membrane properties using a linearized viscoelastic elasto-electrohydrodynamic model. The model can capture plasticity and strain hardening that are otherwise missed in simplified elasticity-based models.

The role of the lipid environment in the activity of G protein coupled receptors

G protein coupled receptors (GPCRs) are a class of membrane proteins that sense extracellular signals ranging from light to odorants and small molecules and activate intracellular signaling pathways that control important physiological responses. Being composed of 7 transmembrane helices linked by extracellular and intracellular loops, the great majority of the sequence of these receptors is embedded in the lipid membrane. Therefore, it is expected GPCR structure and function to be impacted by the surrounding lipid environment and the lipid membrane physico-chemical and mechanical properties. A large number of examples from the literature is provided to highlight the role of the lipid nature (lipid headgroup, membrane polyunsaturation and cholesterol) and membrane physical and mechanical properties (curvature elastic stress, membrane thickness and hydrophobic mismatch, fluidity) in the activity of different GPCRs. In addition, lipids are important co-factors being identified in very specific locations in several GPCR structures. GPCRs and G proteins can also be lipid post-translationally modified and such events can significantly impact membrane binding, trafficking and signaling. These aspects are all treated in this review. Understanding how the lipid can modulate GPCR activity is important not only from a fundamental point of view but also due to the fact that certain pathologies, where GPCRs are central targets, have been associated with important lipid imbalance. Establishing a link between the lipid pathological imbalance and the receptor functioning in such environment is thus essential as it can open avenues to potentially innovative therapeutic strategies.

Fabrication of mixed nanoceramic waste with polymeric matrix membranes for water desalting

Abstract Mixed matrix membranes were prepared by blending technique between nanoceramic powder and polyethersulfone. Nanoceramic powder (NC) as a fine powder was produced from ceramic industries. The effect of NC as an additive on the membrane matrix was studied. Increasing in NC% on polymeric blend enhances the membrane mechanical properties, where the tensile strength was 13.92 MPa with elongation of 23.67 mm for prepared blend membrane with NC 1 wt%. The highest salt rejection was about 89.3% with permeate flux of 34.6 L/m2 h for R1 membrane using NS of percentage 4 wt% and nonwoven polyester support. The increase in NS% to 6 wt % leads to an increase in the salt rejection to 94.2% after 1 h operating time. The coating was achieved using the layer by layer technique which was carried out on the membrane surface to improve the salt rejection percentage. The salt rejection was found to reach about 99.8% after such coating process; but for permeate flux, it shows a certain decrease. The flux of membrane before the coating was 23.4 L/m2 h for R2 membrane (1 wt% NC & 6 wt% NS), while after coating the flux was reduced to reach 21.6 L/m2 h.

A Novel Methodology to Obtain the Mechanical Properties of Membranes by Means of Dynamic Tests.

A new, non-destructive methodology is proposed in this work in order to determine the mechanical properties of membrane using vibro-acoustic tests. This procedure is based on the dynamic analysis of the behavior of the membrane. When the membrane is subjected to a sound excitation it responds by vibrating based on its modal characteristics and this modal parameter is directly related to its mechanical properties. The paper is structured in two parts. First, the theoretical bases of the test are presented. The interaction between the sound waves and the membrane (mechano-acoustic coupling) is complex and requires meticulous study. It was broadly studied by means of numerical simulations. A summary of this study is shown. Aspects, such as the position of the sound source, the measuring points, the dimensions of the membrane, the frequency range, and the magnitudes to be measured, among others, were evaluated. The validity of modal analysis curve-fitting techniques to extract the modal parameter from the data measures was also explored. In the second part, an experimental test was performed to evaluate the validity of the method. A membrane of the same material with three different diameters was measured with the aim of estimating the value of the Young’s modulus. The procedure was applied and satisfactory results were obtained. Additionally, the experiment shed light on aspects that must be taken account in future experiments.

Highly conductive quaternary ammonium-containing cross-linked poly(vinyl pyrrolidone) for high-temperature PEM fuel cells with high-performance

Poly(vinyl pyrrolidone) (PVP)-based high-temperature polymer electrolyte membranes (HT-PEMs) doped with phosphoric acid (PA) present an attractive prospect for high-temperature fuel cell. However, its proton conductivities and mechanical properties are inversely dependent on PVP content in membranes. Herein, chloromethyl-polysulfone is used as a polymeric crosslinker to fabricate cross-linked PVP. The effects of chloromethylation degree of polysulfone on PVP cross-linking degree, free volume and other parameters are studied. The quaternary amine groups introduced by cross-linking reaction enhances PA adsorption and retention capacity of membrane. The increased molar free volume created by polymeric crosslinker can accommodate more PA storage and reduce the polymer main chain plasticization. Thus, the mechanical properties of membranes are maintained. When compared to uncross-linked C-PVP-0/PA, the cross-linked C-PVP-13.7%/PA exhibits improved mechanical strength with increasement of 140% (4.5 MPa) and enhanced proton conductivity with increasement of 119% (120.0 mS cm−1@160 °C). Also, these superior characteristics allow a significantly enhanced H2–O2 fuel cell performance with the membrane of 724.9 mW cm−2 @160 °C, which has increasement of 50% in comparison with that of the C-PVP-0%/PA membrane, and excellent durability. These praiseworthy results suggest that the cross-linked membrane within moderately molar free volume is potential to act as HT-PEMs materials for real-world applications.

Flat sheet metakaolin ceramic membrane for water desalination via direct contact membrane distillation

Abstract Hydrophobic metakaolin-based flat sheet membrane was developed via phase inversion and sintering technique and modified through 1H,1H,2H,2H-perfluorooctyltriethoxysilane grafting agents. The prepared membrane was characterized by different techniques such as XRD, FTIR, SEM, contact angle, porosity, and mechanical strength. Their results indicated that the wettability, structural, and mechanical properties of the prepared membrane confirm the suitability of the material for membrane distillation (MD) application. The prepared metakaolin-based flat sheet membrane acquired hydrophobic properties after surface modification with the water contact angle values of 113.2° to 143.3°. Afterward, the membrane performance was tested for different sodium chloride aqueous solutions (synthetic seawater) and various operating parameters (feed temperature, feed flow rate) using direct contact membrane distillation (DCMD). Based on the findings, the prepared membrane at metakaolin loading of 45 wt.% and sintered at 1,300 °C was achieved the best performance with >95% salt rejection and permeate flux of 6.58 ± 0.3 L/m2 · h at feed temperature of 80 °C, feed concentration of 35 g/L, and feed flow rate of 60 L/h. It can be concluded that further optimization of membrane porosity, mechanical, and surface properties is required to maximize the permeate flux and salt rejection.

Enhanced polysulfone ultrafiltration membrane performance through fullerol Addition: A study towards optimization

In this study, we have prepared and characterized polysulfone (PSF) ultrafiltration membranes, via a phase inversion method, which incorporate oxidized fullerenes (fullerols as C60(OH)x(ONa)y, with x + y = 24 and y = 6 to 8). Fullerol addition, at relatively low loadings (≤2.5 wt%), has significant impact on the resulting membrane structure, permeability, anti-fouling, and mechanical properties. Fullerol modified membranes have enlarged, open-ended pores and enhanced (surface) hydrophilicity. When optimized, incorporation of fullerol breaks the traditional trade-off between membrane permeability and selectivity (i.e., rejection of bovine serum albumin (BSA)), as both are improved with 1.5% fullerol (wt/wt), from 23.9 to 191.9 LMHB and 89% to 93%, respectively. Recovery measurements and protein adsorption tests also indicate that anti-fouling properties are enhanced via fullerol incorporation, which is likely due to decreased membrane roughness and increased surface-based electrostatic repulsion. Mechanical strength measurements indicate an optimal incorporation ratio at 0.5% fullerol/PSF (w/w). Taken together, results clearly demonstrate the potential of fullerol as a novel and effective, yet simple, PSF membrane modifier.

Effect of the mechanical properties of the cell membrane on the transition energy barrier of electroporation

The mechanical properties of the cell membrane play an important role in electroporation. This paper studied the influence of the mechanical properties of the cell membrane on the transition energy of electroporation through both modeling and experiments. An electromechanical coupling model of a single pore on the cell membrane was established in COMSOL, and the effect of elastic strain energy on the formation of pores was analyzed. Additionally, to compare the transition energy barrier of pores for different elastic properties of the cell membrane, electroporation experiments were carried out at different temperatures. The simulation showed that the elastic strain energy of the cell membrane increased the transition energy barrier of the pores. The experiments also showed that the transition energy barrier was larger when the elasticity of the cell membrane is intact, which was in good agreement quantitatively with the simulation results. We demonstrated that the mechanical properties of the cell membrane hinder the pore formation, which may be due to the increase of the transition energy barrier. We analyzed the possible mechanism of the effect of cell membrane mechanical properties on electroporation and found the contribution of cell membrane mechanical properties to electroporation during the delivery of exogenous substances, which can provide guidance for improving therapies in electrochemotherapy.

Identification of electroporation sites in the complex lipid organization of the plasma membrane.

The plasma membrane of a biological cell is a complex assembly of lipids and membrane proteins, which tightly regulate transmembrane transport. When a cell is exposed to strong electric field, the membrane integrity becomes transiently disrupted by formation of transmembrane pores. This phenomenon termed electroporation is already utilized in many rapidly developing applications in medicine including gene therapy, cancer treatment, and treatment of cardiac arrhythmias. However, the molecular mechanisms of electroporation are not yet sufficiently well understood; in particular, it is unclear where exactly pores form in the complex organization of the plasma membrane. In this study, we combine coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis to identify how formation of pores depends on the local lipid organization. We show that pores do not form homogeneously across the membrane, but colocalize with domains that have specific features, the most important being high density of polyunsaturated lipids. We further show that knowing the lipid organization is sufficient to reliably predict poration sites with machine learning. Additionally, by analysing poration kinetics with Bayesian survival analysis we show that poration does not depend solely on local lipid arrangement, but also on membrane mechanical properties and the polarity of the electric field. Finally, we discuss how the combination of atomistic and coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis can guide the design of future experiments and help us to develop an accurate description of plasma membrane electroporation on the whole-cell level. Achieving this will allow us to shift the optimization of electroporation applications from blind trial-and-error approaches to mechanistic-driven design.

Voltage-Driven Alterations to Neuron Viscoelasticity.

The consideration of neurons as coupled mechanical-electrophysiological systems is supported by a growing body of experimental evidence, including observations that cell membranes mechanically deform during the propagation of an action potential. However, the short-term (seconds to minutes) influence of membrane voltage on the mechanical properties of a neuron at the single-cell level remains unknown. Here, we use microscale dynamic mechanical analysis to demonstrate that changes in membrane potential induce changes in the mechanical properties of individual neurons. We simultaneously measured the membrane potential and mechanical properties of individual neurons through a multiphysics single-cell setup. Membrane voltage of a single neuron was measured through whole-cell patch clamp. The mechanical properties of the same neuron were measured through a nanoindenter, which applied a dynamic indentation to the neuron at different frequencies. Neuronal storage and loss moduli were lower for positive voltages than negative voltages. The observed effects of membrane voltage on neuron mechanics could be due to piezoelectric or flexoelectric effects and altered ion distributions under the applied voltage. Such effects could change cell mechanics by changing the intermolecular interactions between ions and the various biomolecules within the membrane and cytoskeleton.

Synergistic effect of hybridized TNT@GO fillers in CTA-based mixed matrix membranes for selective CO2/CH4 separation

Titanium dioxide nanotube (TNT) amalgamated graphene oxide (GO) matrix was blended with cellulose triacetate (CTA) polymer to form a new kind of mixed matrix membranes (MMMs) for the selective biogas upgrading. The effect of hybrid fillers on the physico-chemical, thermal and mechanical properties of membranes were studied using different spectroscopic techniques. Notable improvements on these properties were observed on MMMs as compared to the pristine membrane. Similarly, resulting MMMs exhibited higher CO2 adsorption affinity. Furthermore, single gas permeation measurements revealed higher permeability as well as selectivity for [email protected]/CTA membrane. CO2 permeability increased almost 7 times, reaching 22.54 Barrer, whereas CO2/CH4 selectivity increased nearly three folds from 25.06 for the pristine membrane to 86.69 for [email protected]/CTA membrane and reached the Robeson 2008 upper bound. The long term stability experiment of the [email protected]/CTA membrane confirm the anti-aging ability suggesting its practical application in the bio/natural gas upgrading process. These results established an effective modification approach for applying alternative porous hybrid fillers into gas separation applications.

Polyunsaturated fatty acids differentially modulate membrane elasticity in membranes containing high cholesterol

Membrane composition is important for the function of membrane proteins including ion channels and membrane-embedded receptors. One class of proteins that are especially sensitive to membrane composition are mechanosensitive channels, which activate in response to changes in membrane tension. Recently, polyunsaturated fatty acids (PUFAs) were demonstrated to alter mechanosensitive channel behavior, but the mechanism for these observations remains unknown. Mechanosensitive channel behavior is expected to be dependent on membrane mechanical properties such as the membrane area expansion modulus (Ka), which measures the extent to which membrane tension exerts a change in bilayer area.