Lipid Packing Research Articles

What different physical techniques can disclose about disruptions on membrane structure caused by the antimicrobial peptide Hylin a1 and a more positively charged analogue

The present work monitors structural changes in anionic membranes (DPPG; 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol)) caused by the native antimicrobial peptide (AMP) Hylin a1 (Hya1; IFGAILPLALGALKNLIK-NH2) and its synthetic analogue K0Hya1 (KIFGAILPLALGALKNLIK-NH2), with an extra positive residue of lysine at the N-terminus of the peptide chain. Anionic membranes were used to mimic anionic lipids in bacteria membranes. Differential scanning calorimetry (DSC) evinced that both peptides strongly disrupt the lipid bilayers. However, whereas the native peptide (+3) induces a space-average and/or time-average disruption on DPPG bilayers, the more charged, K0Hya1 (+4), appears to be strongly attached to the membrane, clearly giving rise to the coexistence of two different lipid regions, one depleted of peptide and another one peptide-disrupted. The membrane fluorescent probe Laurdan indicates that, in average, the peptides increase the bilayer packing of fluid DPPG (above the lipid gel-fluid transition temperature) and/or decrease its polarity. Spin labels, incorporated into DPPG membrane, confirm, and extend the results obtained with Laurdan, indicating that the peptides increase the lipid packing both in gel and fluid DPPG bilayers. Therefore, our results confirm that Laurdan is often unable to monitor structural modifications induced on gel membranes by exogenous molecules. Through the measurement of the leakage of entrapped carboxyfluorescein (CF), a fluorescent dye, in DPPG large unilamellar vesicles it was possible to show that both peptides induce pore formation in DPPG bilayers. Furthermore, CF experiments show that Hylin peptides are strongly bound to DPPG bilayers in the gel phase, not being able to migrate to other DPPG vesicles. Here we discuss the complementarity of different techniques in monitoring structural alterations caused on lipid bilayers by Hylin peptides, and how it could be used to help in the understanding of the action of other exogenous molecules on biological membranes.

Lipid Packing in Cell Membrane and Intracellular Delivery

Lipid Packing in Cell Membrane and Intracellular Delivery

Biophysical analysis of gelatin and PLGA nanoparticle interactions with complex biomimetic lung surfactant models.

Biocompatible materials are increasingly used for pulmonary drug delivery, and it is essential to understand their potential impact on the respiratory system, notably their effect on lung surfactant, a monolayer of lipids and proteins, responsible for preventing alveolar collapse during breathing cycles. We have developed a complex mimic of lung surfactant composed of eight lipids mixed in ratios reported for native lung surfactant. A synthetic peptide based on surfactant protein B was added to better mimic the biological system. This model was used to evaluate the impact of biocompatible gelatin and poly(lactic-co-glycolic acid) nanoparticles. Surface pressure-area isotherms were used to assess lipid packing, film compressibility and stability, whereas the lateral organization was visualized by Brewster angle microscopy. Nanoparticles increased film fluidity and altered the monolayer collapse pressure. Bright protruding clusters formed in their presence indicate a significant impact on the lateral organization of the surfactant film. Altogether, this work indicates that biocompatible materials considered to be safe for drug delivery still need to be assessed for their potential detrimental impact before use in therapeutic applications.

Quantitative Measurements of Membrane Lipid Order in Yeast and Fungi.

Membrane lateral heterogeneity, historically referred to as the lipid raft hypothesis, has been extensively investigated through physiochemical experiments on model membranes. Currently, the basic principles are well understood; however, the physiological relevance of these structures in living organisms is still not clear. Thus, studying membrane organization in vivo is extremely important and elucidates the role of such structures in various membrane-associated processes. This is particularly true when a whole single-celled organism can be studied rather than an isolated cell. The ordered and disordered membrane phases are characterized by the degree of acyl chain packing in the lipid bilayer. Polar water molecules can penetrate into the low-density lipid packing of the disordered phase, but are more excluded from the tightly packed ordered phase. Here, polarity-sensitive probes, embedded in the lipid bilayer, are used to report on membrane organization and to quantitate this parameter via 2-channel fluorescence microscopy. Coupling genetic approaches, which are easily accessible in yeast model organisms, with the imaging approach described here provides a great opportunity to investigate how membrane heterogeneity impacts physiology.

Chemistry of Lipid Nanoparticles for RNA Delivery.

Lipid nanoparticles (LNPs) are a type of lipid vesicles that possess a homogeneous lipid core. These vesicles are widely used in small-molecule drug and nucleic acid delivery and recently gained much attention because of their remarkable success as a delivery platform for COVID-19 mRNA vaccines. Nonetheless, the utility of transient protein expression induced by mRNA extends far beyond vaccines against infectious diseases─they also hold promise as cancer vaccines, protein replacement therapies, and gene editing components for rare genetic diseases. However, naked mRNA is inherently unstable and prone to rapid degradation by nucleases and self-hydrolysis. Encapsulation of mRNA within LNPs protects mRNA from extracellular ribonucleases and assists with intracellular mRNA delivery.In this Account, we discuss the core features of LNPs for RNA delivery. We focus our attention on LNPs designed to deliver mRNA; however, we also include examples of siRNA-LNP delivery where appropriate to highlight the commonalities and the dissimilarities due to the nucleic acid structure. First, we introduce the concept of LNPs, the advantages and disadvantages of utilizing nucleic acids as therapeutic agents, and the general reasoning behind the molecular makeup of LNPs. We also briefly highlight the most recent clinical successes of LNP-based nucleic acid therapies. Second, we describe the theory and methods of LNP self-assembly. The common idea behind all of the preparation methods is inducing electrostatic interactions between the nucleic acid and charged lipids and promoting nanoparticle growth via hydrophobic interactions. Third, we break down the LNP composition with special attention to the fundamental properties and purposes of each component. This includes the identified molecular design criteria, commercial sourcing, impact on intracellular trafficking, and contribution to the properties of LNPs. One of the key components of LNPs is ionizable lipids, which initiate electrostatic binding with endosomal membranes and facilitate cytosolic release; however, the roles of other lipid components should not be disregarded, as they are associated with stability, clearance, and distribution of LNPs. Fourth, we review the attributes of LNP constructs as a whole that can heavily influence RNA delivery. These attributes are LNP size, charge, internal structure, lipid packing, lipid membrane hydration, stability, and affinity toward biomacromolecules. We also discuss the specific techniques used to examine these attributes and how they can be adjusted. Finally, we offer our perspective on the future of RNA therapies and some questions that remain in the realm of LNP formulation and optimization.

The highly packed and dehydrated structure of preformed unexposed human pulmonary surfactant isolated from amniotic fluid.

By coating the alveolar air-liquid interface, lung surfactant overwhelms surface tension forces that, otherwise, would hinder the lifetime effort of breathing. Years of research have provided a picture of how highly hydrophobic and specialized proteins in surfactant promote rapid and efficient formation of phospholipid-based complex three-dimensional films at the respiratory surface, highly stable under the demanding breathing mechanics. However, recent evidence suggests that the structure and performance of surfactant typically isolated from bronchoalveolar lung lavages may be far from that of nascent, still unused, surfactant as freshly secreted by type II pneumocytes into the alveolar airspaces. In the present work, we report the isolation of lung surfactant from human amniotic fluid (amniotic fluid surfactant, AFS) and a detailed description of its composition, structure, and surface activity in comparison to a natural surfactant (NS) purified from porcine bronchoalveolar lavages. We observe that the lipid/protein complexes in AFS exhibit a substantially higher lipid packing and dehydration than in NS. AFS shows melting transitions at higher temperatures than NS and a conspicuous presence of nonlamellar phases. The surface activity of AFS is not only comparable with that of NS under physiologically meaningful conditions but displays significantly higher resistance to inhibition by serum or meconium, agents that inactivate surfactant in the context of severe respiratory pathologies. We propose that AFS may be the optimal model to study the molecular mechanisms sustaining pulmonary surfactant performance in health and disease, and the reference material to develop improved therapeutic surfactant preparations to treat yet unresolved respiratory pathologies.

Demolish and Rebuild: Controlling Lipid Self-Assembly toward Triggered Release and Artificial Cells.

The ability to modulate the structures of lipid membranes, predicated on our nuanced understanding of the properties that drive and alter lipid self-assembly, has opened up many exciting biological applications. In this Perspective, we focus on two endeavors in which the same principles are invoked to achieve completely opposite results. On one hand, controlled liposome decomposition enables triggered release of encapsulated cargo through the development of synthetic lipid switches that perturb lipid packing in the presence of disease-associated stimuli. In particular, recent approaches have utilized artificial lipid switches designed to undergo major conformational changes in response to a range of target conditions. On the other end of the spectrum, the ability to drive the in situ formation of lipid bilayer membranes from soluble precursors is an important component in the establishment of artificial cells. This work has culminated in chemoenzymatic strategies that enable lipid manufacturing from simple components. Herein, we describe recent advancements in these two unique undertakings that are linked by their reliance on common principles of lipid self-assembly.

Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles.

Fusion events in living cells are intricate phenomena that require the coordinate action of multicomponent protein complexes. However, simpler synthetic tools to control membrane fusion in artificial cells are highly desirable. Native membrane fusion machinery mediates fusion, driving a delicate balance of membrane curvature and tension between two closely apposed membranes. Here, we show that silica nanoparticles (SiO2 NPs) at a size close to the cross-over between tension-driven and curvature-driven interaction regimes initiate efficient fusion of biomimetic model membranes. Fusion efficiency and mechanisms are studied by Förster resonance energy transfer and confocal fluorescence microscopy. SiO2 NPs induce a slight increase in lipid packing likely to increase the lateral tension of the membrane. We observe a connection between membrane tension and fusion efficiency. Finally, real-time confocal fluorescence microscopy reveals three distinct mechanistic pathways for membrane fusion. SiO2 NPs show significant potential for inclusion in the synthetic biology toolkit for membrane remodeling and fusion in artificial cells.

Blood bank storage of red blood cells increases RBC cytoplasmic membrane order and bending rigidity.

Blood banks around the world store blood components for several weeks ensuring its availability for transfusion medicine. Red blood cells (RBCs) are known to undergo compositional changes during storage, which may impact the cells’ function and eventually the recipients’ health. We extracted the RBC’s cytoplasmic membrane (RBCcm) to study the effect of storage on the membranes’ molecular structure and bending rigidity by a combination of X-ray diffraction (XRD), X-ray diffuse scattering (XDS) and coarse grained Molecular Dynamics (MD) simulations. Blood was stored in commercial blood bags for 2 and 5 weeks, respectively and compared to freshly drawn blood. Using mass spectrometry, we measured an increase of fatty acids together with a slight shift towards shorter tail lengths. We observe an increased fraction (6%) of liquid ordered (lo) domains in the RBCcms with storage time, and an increased lipid packing in these domains, leading to an increased membrane thickness and membrane order. The size of both, lo and liquid disordered (ld) lipid domains was found to decrease with increased storage time by up to 25%. XDS experiments reveal a storage dependent increase in the RBCcm’s bending modulus κ by a factor of 2.8, from 1.9 kBT to 5.3 kBT. MD simulations were conducted in the absence of proteins. The results show that the membrane composition has a small contribution to the increased bending rigidity and suggests additional protein-driven mechanisms.

The pore-forming activity of sticholysin I is enhanced by the presence of a phospholipid hydroperoxide in membrane

Sticholysin I (StI) is a pore-forming toxin (PFT) belonging to the actinoporin protein family characterized by high permeabilizing activity in membranes. StI readily associates with sphingomyelin (SM)-containing membranes originating pores that can lead to cell death. Binding and pore-formation are critically dependent on the physicochemical properties of membrane. 1-palmitoyl-2-oleoylphosphatidylcholine hydroperoxide (POPC–OOH) is an oxidized phospholipid (OxPL) containing an –OOH moiety in the unsaturated hydrocarbon chain which orientates towards the bilayer interface. This orientation causes an increase in the lipid molecular area, lateral expansion and decrease in bilayer thickness, elastic and bending modulus, as well as modification of lipid packing. Taking advantage of membrane structural changes promoted by POPC-OOH, we investigated its influence on the permeabilizing ability of StI. Here we report the action of StI on Giant Unilamellar Vesicles (GUVs) made of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and SM containing increasing amount of POPC-OOH to assess vesicle permeability changes when compared to OxPL-lacking membranes. Inclusion of POPC-OOH in membranes did not promote spontaneous vesicle leaking but resulted in increased membrane permeability due to StI action. StI activity did not modify the fluid-gel phase coexistence boundaries neither in POPC:SM or POPC-OOH:SM membranes. However, the StI insertion mechanism in membrane seems to differ between POPC:SM and POPC-OOH:SM mixtures as suggested by changes in the time course of monolayer surface tension measurements, even though a preferable binding of the toxin to OxPL-containing systems could not be here demonstrated. In summary, modifications in the membrane imposed by lipid hydroperoxidation favor StI permeabilizing activity.

Role of Membrane Stretch in Adsorption of Antiviral Peptides onto Lipid Membranes and Membrane Pore Formation.

Many medically important viruses are enveloped viruses, which are surrounded by a structurally conserved, host-derived lipid membrane coating. Agents that target and disrupt this membrane coating could potentially function as broad-spectrum antiviral drugs. The amphipathic α-helical (AH) peptide derived from the N-terminus of the hepatitis C virus NS5A protein is one such candidate and has been demonstrated to be able to selectively rupture lipid vesicles in the size range of viruses (<160 nm diameter). However, the mechanism underlying this membrane curvature selectivity remains elusive. In this study, we have performed molecular dynamics simulations to study the binding of the AH peptide to model membranes that are stretched to resemble the looser lipid headgroup packing present on highly curved outer membranes of nanoscale vesicles. We found that the AH peptide binds more favorably to membranes that are stretched. In addition, a tetrameric placement of peptides across the membrane induced stable pore formation in the stretched membrane. Thus, our results suggest that the AH peptide senses the high curvature of nanoscale vesicles via the enhanced exposure of lipid packing defects induced by membrane area strain.

Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis.

SUMMARYClathrin-mediated endocytosis (CME) is critical for cellular signal transduction, receptor recycling, and membrane homeostasis in mammalian cells. Acute depletion of cholesterol disrupts CME, motivating analysis of CME dynamics in the context of human disorders of cholesterol metabolism. We report that inhibition of post-squalene cholesterol biosynthesis impairs CME. Imaging of membrane bending dynamics and the CME pit ultrastructure reveals prolonged clathrin pit lifetimes and shallow clathrin-coated structures, suggesting progressive impairment of curvature generation correlates with diminishing sterol abundance. Sterol structural requirements for efficient CME include 3′ polar head group and B-ring conformation, resembling the sterol structural prerequisites for tight lipid packing and polarity. Furthermore, Smith-Lemli-Opitz fibroblasts with low cholesterol abundance exhibit deficits in CME-mediated transferrin internalization. We conclude that sterols lower the energetic costs of membrane bending during pit formation and vesicular scission during CME and suggest that reduced CME activity may contribute to cellular phenotypes observed within disorders of cholesterol metabolism.

Dielectric Properties of Phosphatidylcholine Membranes and the Effect of Sugars.

Simple carbohydrates are associated with the enhanced risk of cardiovascular disease and adverse changes in lipoproteins in the organism. Conversely, sugars are known to exert a stabilizing effect on biological membranes, and this effect is widely exploited in medicine and industry for cryopreservation of tissues and materials. In view of elucidating molecular mechanisms involved in the interaction of mono- and disaccharides with biomimetic lipid systems, we study the alteration of dielectric properties, the degree of hydration, and the rotational order parameter and dipole potential of lipid bilayers in the presence of sugars. Frequency-dependent deformation of cell-size unilamellar lipid vesicles in alternating electric fields and fast Fourier transform electrochemical impedance spectroscopy are applied to measure the specific capacitance of phosphatidylcholine lipid bilayers in sucrose, glucose and fructose aqueous solutions. Alteration of membrane specific capacitance is reported in sucrose solutions, while preservation of membrane dielectric properties is established in the presence of glucose and fructose. We address the effect of sugars on the hydration and the rotational order parameter for 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC) and 1-stearoyl-2-oleoyl-sn-glycero-3- phosphocholine (SOPC). An increased degree of lipid packing is reported in sucrose solutions. The obtained results provide evidence that some small carbohydrates are able to change membrane dielectric properties, structure, and order related to membrane homeostasis. The reported data are also relevant to future developments based on the response of lipid bilayers to external physical stimuli such as electric fields and temperature changes.

Developing initial conditions for simulations of asymmetric membranes: a practical recommendation

It has been proposed that the surface tension difference between leaflets (or differential stress) in asymmetric bilayers is generally nonvanishing. This implies that there is no unique approach to generate initial conditions for simulations of asymmetric bilayers in the absence of experimentally derived constraints. Current generation methods include individual area per lipid (APL) based, leaflet surface area (SA) matching, and zero leaflet tension based (0-DS). This work adds a bilayer-based approach that aims for achieving partial chemical equilibrium by interleaflet switching of selected lipids via P21 periodic boundary conditions. Based on a recently proposed theoretical framework, we obtained expressions for tensions in asymmetric bilayers from both the bending and area strains. We also developed a quantitative measure for the energetic penalty from the differential stress. The impacts of APL-, SA-, and 0-DS-based approaches on mechanical properties are assessed for two different asymmetric bilayers. The lateral pressure profile and its moments differ significantly for each method, whereas the area compressibility modulus is relatively insensitive. Application of P21 periodic boundary conditions (APL/P21, SA/P21, and 0-DS/P21) results in better agreement in mechanical properties between asymmetric bilayers generated by APL-, SA-, and 0-DS-based approaches, in which changes are the smallest for bilayers from the SA-based method. The estimated differential stress from the theory shows good agreement with that from the simulations. These simulation results and the good agreement between the predicted and observed differential stress further support the theoretical framework in which bilayer mechanical properties are outcomes of the interplay between intrinsic bending and asymmetric lipid packing. Based on the simulation results and theoretical predictions, the SA/P21-based, or at least the SA-based (when the differential stress is small), approach is recommended as a practical method for developing initial conditions for asymmetric bilayer simulations.

Bipolar Imidazolium-Based Lipid Analogues for Artificial Archaeosomes.

Archaeal lipids have harvested biomedical and biotechnological interest because of their ability to form membranes with low permeability and enhanced temperature and pressure stability. Because of problems in isolating archaeal lipids, chemical synthesis appears to be a suitable means of producing model lipids that mimic the biological counterparts. Here, we introduce a new concept: we synthesized bipolar alkylated imidazolium salts of different chain lengths (BIm10-32) and studied their structure and lyotropic phase behavior. Furthermore, mixtures of the bolalipid analogues with phospholipid model biomembranes of diverse complexity were studied. DSC, fluorescence and FTIR spectroscopy, confocal fluorescence microscopy, DLS, SAXS, and TEM were used to reveal changes in lipid phase behavior, fluidity, the lipid's conformational order, and membrane morphology over a wide range of temperatures and for selected pressures. It could be shown that the long-chain BImN32 can form monolayer sheets. Integrated in phospholipid membranes, it reveals a fluidizing effect. Here, the two polar head groups, connected by a long alkyl chain, enable the integration into the bilayer. Interestingly, addition of BImN32 to fluid DPPC liposomes increased the lipid packing markedly, rendering the membrane system more stable at higher temperatures. The membrane system is also stable against compression as indicated by the high-pressure stability of the system, mimicking an archaeal lipid-like behavior. BImN32 incorporation into raft-like anionic model biomembranes led to marked changes in lateral membrane organization, topology, and fusogenicity of the membrane. Overall, it was found that long-chain imidazolium-based bolalipid analogues can help adjust membrane's biophysical properties, while the imidazolium headgroup provides the ability for crucial electrostatic interaction for vesicle fusion or selective interaction with membrane-related signaling molecules and polypeptides in a synthetically tractable manner. The results obtained may help to develop new approaches for rational design of extremophilic bolalipid-based liposomes for various applications, including delivery of drugs and vaccines.

Long-term STED imaging of membrane packing and dynamics by exchangeable polarity-sensitive dyes

Understanding the plasma membrane nanoscale organization and dynamics in living cells requires microscopy techniques with high spatial and temporal resolution that permit for long acquisition times and allow for the quantification of membrane biophysical properties, such as lipid ordering. Among the most popular super-resolution techniques, stimulated emission depletion (STED) microscopy offers one of the highest temporal resolutions, ultimately defined by the scanning speed. However, monitoring live processes using STED microscopy is significantly limited by photobleaching, which recently has been circumvented by exchangeable membrane dyes that only temporarily reside in the membrane. Here, we show that NR4A, a polarity-sensitive exchangeable plasma membrane probe based on Nile red, permits the super-resolved quantification of membrane biophysical parameters in real time with high temporal and spatial resolution as well as long acquisition times. The potential of this polarity-sensitive exchangeable dye is showcased by live-cell real-time three-dimensional STED recordings of bleb formation and lipid exchange during membrane fusion as well as by STED-fluorescence correlation spectroscopy experiments for the simultaneous quantification of membrane dynamics and lipid packing that correlate in model and live-cell membranes.

Probing the Formation and Conformational Relaxation of Previtamin D3 and Analogues in Solution and in Lipid Bilayers.

The photosynthesis of vitamin D3 in mammalian skin results from UV-B irradiation of provitamin D3 (7-dehydrocholesterol, DHC) at ca. 290 nm. Upon return to the ground state, the hexatriene product, previtamin D3, undergoes a conformational equilibration between helical gZg and more planar tZg and tZt forms. The helical gZg forms provide a pathway for the formation of vitamin D3 via a [1,7]-sigmatropic hydrogen shift. Steady state photolysis and UV transient absorption spectroscopy are combined to explore the conformational relaxation of previtamin D3 formed from DHC in isotropic solution and confined to lipid bilayers chosen to model the biological cell membrane. The results are compared with measurements for two analogues: previtamin D2 formed from ergosterol (provitamin D2) and previtamin D3 acetate formed from DHC acetate. The resulting spectral dynamics are interpreted in the context of simulations of optical excitation energy and oscillator strength as a function of conformation. In solution, the relaxation dynamics and steady state product distributions of the three compounds are nearly identical, favoring tZg forms. When confined to lipid bilayers, the heterogeneity and packing forces alter the conformational distributions and enhance the population of a gZg conformer capable of vitamin D formation.

Reprogrammed lipid metabolism protects inner nuclear membrane against unsaturated fat.

SummaryThe cell nucleus is surrounded by a double membrane. The lipid packing and viscosity of membranes is critical for their function and is tightly controlled by lipid saturation. Circuits regulating the lipid saturation of the outer nuclear membrane (ONM) and contiguous endoplasmic reticulum (ER) are known. However, how lipid saturation is controlled in the inner nuclear membrane (INM) has remained enigmatic. Using INM biosensors and targeted genetic manipulations, we show that increased lipid unsaturation causes a reprogramming of lipid storage metabolism across the nuclear envelope (NE). Cells induce lipid droplet (LD) formation specifically from the distant ONM/ER, whereas LD formation at the INM is suppressed. In doing so, unsaturated fatty acids are shifted away from the INM. We identify the transcription circuits that topologically reprogram LD synthesis and identify seipin and phosphatidic acid as critical effectors. Our study suggests a detoxification mechanism protecting the INM from excess lipid unsaturation.

Surface and Bulk Modifications of Fibrous Erionite in Mimicked Gamble’s Solution at Acidic pH

This study aimed at investigating both the surface and bulk modifications occurring on fibrous erionite during leaching in a mimicked Gamble’s solution (MGS) at pH of 4.5 and T = 37 °C, up to one month of incubation. Samples were characterized by a multi-analytical approach: field-emission scanning electron microscopy (FE-SEM) was employed to investigate the morphological changes of both pristine and reacted fibres, inductively coupled plasma optical emission spectrometry (ICP-OES) was used to measure the concentration of the released cations; X-ray photoelectron spectroscopy (XPS) was exploited for highlighting possible modifications of surface chemistry; X-ray powder diffraction (XRPD) and high-resolution transmission electron microscopy (HR-TEM) were applied aiming to get information on the structural state of the fibres following the incubation. ICP results integrated with those obtained by both bulk- and surface-chemical characterization highlighted that erionite binds Na especially in the first 24 h of sample incubation in the MGS, following ion exchange with the extra framework cations, in particular Ca. Moreover, our new results show that the Na binding process caused structural modifications with the migration of Na toward the Ca2 site and redistribution of the cations within the erionite cage. TEM investigation pointed out that the interaction between erionite and MGS results in the formation of a new surface amorphous layer with an irregular lobate pattern on an earlier surface weathered layer. However, the silicate framework is not weakened by incubation in the MGS at acidic pH. In addition, on the basis of the Si release normalized to the mineral surface area, fibrous erionite resulted significantly more biodurable than amphibole asbestos. Notably, considering the primary role played by biodurability in inducing pathogenicity, this result certainly supports in vivo observations showing that erionite is much more tumorigenic than asbestos. Moreover, the ions released by erionite when immersed in MGS may trigger biological effects, such as those on lipid packing and membrane permeability. On this basis, we expect a regulatory definition that would provide protection from this carcinogenic fibre.

Di-4-ANEPPDHQ probes the response of lipid packing to the membrane tension change in living cells

Membrane tension plays a significant role in many cellular processes including cell adhesion, migration and spreading. Despite the importance of membrane tension, it remains difficult to measure in vivo. Recently, the development of non-invasive fluorescent probes have made great progress, especially excited-state deplanarization in molecular rotors has been applied to image membrane tension in living cells. Nevertheless, an intrinsic limitation of such kind of probe is that they depend on the lipid packing, and how the lipid packing responds to the membrane tension change remains unclear. Therefore, in this work, we used a polarity-sensitive membrane probe to investigate the possible response mechanism of lipid packing to the change of membrane tension that was regulated by osmotic shocks. The results showed that an increase in membrane tension could stretch the lipids apart with large displacements, and this change was not homogeneous on the whole membrane, instead, increase of membrane tension induced phase separation.