Bilayer Vesicles Research Articles

A Review of Labeling Approaches Used in Small Extracellular Vesicles Tracing and Imaging.

Small extracellular vesicles (sEVs), a subset of extracellular vesicles (EVs) originating from the endosomal compartment, are a kind of lipid bilayer vesicles released by almost all types of cells, serving as natural carriers of nucleic acids, proteins, and lipids for intercellular communication and transfer of bioactive molecules. The current findings suggest their vital role in physiological and pathological processes. Various sEVs labeling techniques have been developed for the more advanced study of the function, mode of action, bio-distribution, and related information of sEVs. In this review, we summarize the existing and emerging sEVs labeling techniques, including fluorescent labeling, radioisotope labeling, nanoparticle labeling, chemical contrast agents labeling, and label-free technique. These approaches will pave the way for an in-depth study of sEVs. We present a systematic and comprehensive review of the principles, advantages, disadvantages, and applications of these techniques, to help promote applications of these labeling approaches in future research on sEVs.

Dynamics of fluid bilayer vesicles: Soft meshes and robust curvature energy discretization.

Continuum models like the Helfrich Hamiltonian are widely used to describe fluid bilayer vesicles. Here we study the molecular dynamics compatible dynamics of the vertices of two-dimensional meshes representing the bilayer, whose in-plane motion is only weakly constrained. We show (i) that Jülicher's discretization of the curvature energy offers vastly superior robustness for soft meshes compared to the commonly employed expression by Gommper and Kroll and (ii) that for sufficiently soft meshes, the typical behavior of fluid bilayer vesicles can emerge even if the mesh connectivity remains fixed throughout the simulations. In particular, soft meshes can accommodate large shape transformations, and the model can generate the typical ℓ^{-4} signal for the amplitude of surface undulation modes of nearly spherical vesicles all the way up to the longest wavelength modes. Furthermore, we compare results for Newtonian, Langevin, and Brownian dynamics simulations of the mesh vertices to demonstrate that the internal friction of the membrane model is negligible, making it suitable for studying the internal dynamics of vesicles via coupling to hydrodynamic solvers or particle-based solvent models.

An electrochemical aptasensor for exosomes based on strand displacement amplification and hybridization chain reaction amplification

Exosomes are lipid bilayer vesicles, relating to the happening and progress of cancer. However, exploring reliable, convenient and sensitive exosomes detection methods in early cancer diagnosis is still challenging. Here, an electrochemical aptasensor based on both signal amplifications of strand displacement amplification (SDA) and hybridization chain reaction (HCR) was developed to sensitively detect tumor exosomes. Firstly, exosomes were recognized by CD63 aptamer, and converted into DNA concentration by chain replacement reaction and magnetic separation. A produced DNA fragment (P) was obtained by SDA，then P was captured at the modified gold electrode and amplified using HCR. Abundant horseradish peroxidase (HRP) attached to DNA concatemers and catalyzed the oxidation of o-phenylenediamine (OPD). The reduction current of 2,3-diaminopenazine (DAP) was measured and the exosomes were quantized. Under the optimal conditions, the DPV response showed a great linear relationship with exosomes concentration range of 44 ∼ 8.8 × 106 particle/μL. The limit of detection was 18 particle/μL. Experimental results show that this is an alternative method to detect exosomes and other tumor markers.

Morphological Transitions in Solutions of Macromolecules with Solvophilic Backbone and Orientationally Mobile Solvophobic Side Groups

A theoretical model describing the self-assembly in dilute solutions of amphiphilic macromolecules containing the backbone built of the solvophilic units (the P groups) and the solvophobic side chains (the H groups) possessing orientational mobility relative to the backbone units has been elaborated. In the framework of strong segregation limit (The size of the insoluble regions of the formed micelles is on the order of the hydrophobic side chains), state diagrams of the solution have been calculated with and without accounting for the orientational entropy contribution of the side groups to the total free energy of the solution at different thermodynamic qualities of solvent for the macromolecules and the grafting density of the H groups; the regions of stability of spherical and cylindrical micelles as well as planar bilayers (vesicles) have been revealed. It has been found that the contribution of the orientational entropy significantly affects the view of the state diagrams. In the case of considering the orientational mobility, the conditions of the cylindrical micelle stability are very sensitive to the change in the grafting density of the side groups. This sensitivity can be the reason why the formation of long cylindrical (wormlike) micelles is not observed in experiments and computer simulations. As earlier demonstrated at a qualitative level, the orientational mobility of the side groups can lead to the emergence of the orientation-induced attraction between the polymer micelles (A. I. Buglakov, D. E. Larin, and V. V. Vasilevskaya, Polymer 232, 124160 (2021)). In this study, exact analytical calculations of the energy of orientation-induced attraction for the case of the interaction between two planar bilayer micelles has been performed. At distances being of the order of the size of the side H group, the orientation-induced attraction forces are much stronger than the van der Waals forces and, hence, the orientation-induced attraction can be decisive in the formation of large aggregates observed in experiments.

Synergism and molecular mismatch in rhamnolipid/CTAC catanionic surfactant mixtures

Rhamnolipids represent a promising class of biosurfactants, whose industrial exploitation could potentially reduce the ecological impact of surfactant-based formulations. In this direction, the rational design of rhamnolipid mixtures with other surfactants constitutes a strategic field of research.In this work, we combine mono-rhamnolipid (mRha) with the cationic surfactant cetyltrimethylammonium chloride (CTAC). The study is conducted at pH = 7.1, so that the mRha carboxylic group is dissociated and catanionic mRha-CTAC mixtures form. The system is investigated across the entire composition range by surface tension and conductivity measurements, which show a strong synergism between the two surfactants in forming mixed aggregates, specifically in mRha-rich mixtures. No coacervation or precipitation is observed, due to the strong asymmetry between the surfactant molecular architectures, with mRha presenting a bulky headgroup and two relatively short tails compared to the single long tail of CTAC. Dynamic Light Scattering (DLS) and Small Angle Neutron Scattering (SANS) experiments show that, while the single surfactants predominantly form small micelles, their mixing results in the spontaneous formation of vesicles. Within the vesicle bilayer, the termini of the longer surfactant tails fold, assuming disordered conformations, as probed by Electron Paramagnetic Resonance (EPR) measurements.These results point to the rational design of rhamnolipid-based catanionic mixtures as a suitable tool to optimize their structural properties, constituting a solid basis for their practical applications.

L-Phenylalanine Partitioning Mechanisms in Model Biological Membranes.

Time-resolved fluorescence spectroscopy in combination with differential scanning calorimetry (DSC) was used to study the chemical interactions that occur when l-phenylalanine is introduced to solutions containing phosphatidylcholine vesicles. Studies reported in this work address open questions about l-Phe's affinity for lipid vesicle bilayers, the effects of l-Phe partitioning on bilayer properties, l-Phe's solvation within a lipid bilayer, and the amount of l-Phe within that local solvation environment. DSC data show that l-Phe reduces the amount of heat necessary to melt saturated phosphatidylcholine bilayers from their gel to liquid-crystalline state but does not change the transition temperature (Tgel-lc). Time-resolved emission shows only a single l-Phe lifetime at low temperatures corresponding to l-Phe remaining solvated in aqueous solution. At temperatures close to Tgel-lc, a second, shorter lifetime appears that is assigned to l-Phe already embedded within the membrane that becomes hydrated as water starts to permeate the lipid bilayer. This new lifetime is attributed to a conformationally restricted rotamer in the bilayer's polar headgroup region and accounts for up to 30% of the emission amplitude. Results reported for dipalmitoylphosphatidylcholine (DPPC, 16:0) lipid vesicles prove to be general, with similar effects observed for dimyristoylphosphatidylcholine (DMPC, 14:0) and distearoylphosphatidylcholine (DSPC, 18:0) vesicles. Taken together, these results create a complete and compelling picture of how l-Phe associates with model biological membranes. Furthermore, this approach to examining amino acid partitioning into membranes and the resulting solvation forces points to new strategies for studying the structure and chemistry of membrane-soluble peptides and selected membrane proteins.

High unimer concentration and asymmetric bilayer observed in small unilamellar vesicles of mixed surfactants TDMAO/LiPFO.

The mixed surfactant system of tetradecyldimethylamine oxide (TDMAO) and lithium perfluorooctanoate (LiPFO) is known to spontaneously self-assemble into well-defined small unilamellar vesicles. For a quantitative analysis of small-angle x-ray scattering on this model system, we complemented the measurements with densitometry, conductimetry, and contrast-variation small-angle neutron scattering. The analysis points to two main findings: first, the vesicles formed to contain a much higher mole fraction (0.61-0.64) of TDMAO than the bulk sample (0.43) and predicted by Regular Solution Theory (RST, 0.46). In consequence, the unimer concentration of LiPFO is more than 5 times higher than predicted by RST. Second, the vesicle bilayer is asymmetric with a higher fraction of LiPFO on the outside. These findings on a model system should be of broader relevance for the understanding of similar mixed surfactant vesicle systems and thereby also be of importance for their use in a number of applications.

Hydrogen Production from Hydrophobic Ruthenium Dye-Sensitized TiO2 Photocatalyst Assisted by Vesicle Formation.

Dye-sensitized H2 evolution photocatalysts have attracted considerable attention as promising systems for the photochemical generation of H2 from water. In this study, to mimic the reaction field of natural photosynthesis artificially, we synthesized a hydrophobic Ru(II) dye-sensitized Pt-TiO2 nanoparticle photocatalyst, RuC9@Pt-TiO2 (RuC9 = [Ru(dC9bpy)2(H4dmpbpy)]2+; dC9bpy = 4,4'-dinonyl-2,2'-bipyridine, H4dmpbpy = 4,4'-dimethyl phosphonic acid-2,2'-bipyridine), and integrated it into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer vesicle membranes. The photocatalytic H2 production activity in 0.5 M l-ascorbic acid aqueous solution enhanced by more than three times in the presence of DPPC vesicles (apparent quantum yield = 2.11%), whereas such a significant enhancement was hardly observed when the vesicle formation was omitted. These results indicate that the highly dispersed state of the hydrophobic RuC9@Pt-TiO2 nanoparticles in the DPPC bilayer vesicles is a key factor in achieving enhanced photocatalytic H2 production activity in aqueous solution.

Photophysical isomerization of liposomal bilayer-included caffeic acid phenethyl ester leading to membrane dehydration

Caffeic acid phenethyl ester (CAPE) is well known for its prolific biological and pharmaceutical applications. There are plethora of studies on CAPE in context to antimicrobial, antiviral, anti-inflammatory and anticancer activities. It has been applied even to suppress chemotherapy-induced toxicities. However, an important property of CAPE has been so far overlooked, which is its photoinduced cis/trans isomerization. The present study has enlightened upon the detailed photophysical changes and the related physical parameters in CAPE. CAPE, being a membrane binding molecule, has been added to the hydrophobic portion of the bilayer of large unilamelar vesicles (LUVs) made from dimyristoyltrimethylammonium propane (DMTAP) lipids in aqueous buffer (pH 7.4). Absorption of light and conversion of the trans-isomers to the cis-form led to vesicular squeezing followed by expulsion of the penetrated water molecules that hydrated the liposomal membrane.

The Roles of Extracellular Vesicles in the Progression of Renal Cell Carcinoma and Their Potential for Future Clinical Application.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and is thought to originate from renal tubular epithelial cells. Extracellular vesicles (EVs) are nanosized lipid bilayer vesicles that are secreted into extracellular spaces by nearly all cell types, including cancer cells and non-cancerous cells. EVs are involved in multiple steps of RCC progression, such as local invasion, host immune modulation, drug resistance, and metastasis. Therefore, EVs secreted from RCC are attracting rapidly increasing attention from researchers. In this review, we highlight the mechanism by which RCC-derived EVs lead to disease progression as well as the potential and challenges related to the clinical implications of EV-based diagnostics and therapeutics.

Extracellular Vesicles as Potential Therapeutic Messengers in Cancer Management.

A deeper understanding of the communication mechanisms of tumor cells in a tumor microenvironment can improve the development of new therapeutic solutions, leading to a more personalized approach. Recently, the field of extracellular vesicles (EVs) has drawn attention due to their key role in intercellular communication. EVs are nano-sized lipid bilayer vesicles that are secreted by all types of cells and can function as intermediators of intercellular communication with the ability to transfer different cargo (proteins, nucleic acids, sugar…) types among cells. This role of EVs is essential in a cancer context as it can affect tumor promotion and progression and contribute to the pre-metastatic niche establishment. Therefore, scientists from basic, translational, and clinical research areas are currently researching EVs with great expectations due to their potential to be used as clinical biomarkers, which are useful for disease diagnosis, prognosis, patient follow-up, or even as vehicles for drug delivery due to their natural carrier nature. The application of EVs presents numerous advantages as drug delivery vehicles, namely their capacity to overcome natural barriers, their inherent cell-targeting properties, and their stability in the circulation. In this review, we highlight the distinctive features of EVs, their application as efficient drug delivery systems, and their clinical applications.

No Life on this Planet Without PHB

AbstractThe history of discovery byRosetta Reuschof oligo‐ and poly‐β‐hydroxybutyrates (OHBs and PHBs) consisting of less thanca. 150 HB units is described. These ‘short‐chain’ biopolymers can be detected in all living organisms and have numerous physiological activities of fundamental importance for the chemistry of life. The largest are components of ion channels such as Ca2+‐polyphosphate‐PHB (Ca‐PPi‐PHB) in genetically competentE. coliand in mammalian mitochondria. Sequences with chain lengths <ca. 30 occur covalently attached to proteins (post‐translational PHBylation), and methyl esters of the dimer and trimer are used by certain bacteria as highly efficient antioxidants. With synthetic monodisperse OHBs (up to 128mer) our group has contributed structural investigations, and we have shown that OHBs≥16 alone make phospholipid bilayer vesicles permeable to Ca ions. An extensive biochemical analysis of the TRPM8 protein channel, responsible for the sense of heat in our skin, proved to be fully active only when PHBylated. Reasons for the difficulty of detecting OHBs and PHBs are discussed: the polyester chain is highly flexible, and there is ester cleavage by base, acid, nucleophiles,Lewisacids, and heat – in stark contrast to peptides. PHBs may be called a ubiquitous butfleetingspecies in the chemistry of life – worth being appreciated and studied much more intensively in the future! A speculation about PHB's possible role in prebiotic compartmentalization is presented, and recent uses of compartmentalization in organic synthesis are briefly mentioned.Portions of the figures used herein were presented in a lecture at the International Symposium on Biopolymers on September 13, 2022, in Sion (Switzerland).

Tumour-derived extracellular vesicle based vaccines for melanoma treatment

The interest of extracellular vesicles (EVs) in cancer immunotherapy is increasing every day. EVs are lipid bilayer vesicles released by most cells, which contain the molecular signature of their parent cell. Melanoma-derived EVs present antigens specific to this aggressive type of cancer, but they also exert immunomodulatory and pro-metastatic activity. Until now, most reviews focus on the immunoevasive characteristics of tumour-derived EVs, but do not help to overcome the issues related to them. In this review, we describe isolation methods of EVs from melanoma patients and most interesting markers to oversee their effect if they are used as antigen carriers. We also discuss the methods developed so far to overcome the lack of immunogenicity of melanoma-derived EVs, which includes EV modification or adjuvant co-administration. In summary, we conclude that EVs can be an interesting antigen source for immunotherapy development once EV obtaining is optimised and the understanding of the mechanisms behind their multiple effects is further understood.Graphical

Gallocin A, an Atypical Two-Peptide Bacteriocin with Intramolecular Disulfide Bonds Required for Activity.

Streptococcus gallolyticus subsp. gallolyticus (SGG) is an opportunistic gut pathogen associated with colorectal cancer. We previously showed that colonization of the murine colon by SGG in tumoral conditions was strongly enhanced by the production of gallocin A, a two-peptide bacteriocin. Here, we aimed to characterize the mechanisms of its action and resistance. Using a genetic approach, we demonstrated that gallocin A is composed of two peptides, GllA1 and GllA2, which are inactive alone and act together to kill "target" bacteria. We showed that gallocin A can kill phylogenetically close relatives of the pathogen. Importantly, we demonstrated that gallocin A peptides can insert themselves into membranes and permeabilize lipid bilayer vesicles. Next, we showed that the third gene of the gallocin A operon, gip, is necessary and sufficient to confer immunity to gallocin A. Structural modeling of GllA1 and GllA2 mature peptides suggested that both peptides form alpha-helical hairpins stabilized by intramolecular disulfide bridges. The presence of a disulfide bond in GllA1 and GllA2 was confirmed experimentally. Addition of disulfide-reducing agents abrogated gallocin A activity. Likewise, deletion of a gene encoding a surface protein with a thioredoxin-like domain impaired the ability of gallocin A to kill Enterococcus faecalis. Structural modeling of GIP revealed a hairpin-like structure strongly resembling those of the GllA1 and GllA2 mature peptides, suggesting a mechanism of immunity by competition with GllA1/2. Finally, identification of other class IIb bacteriocins exhibiting a similar alpha-helical hairpin fold stabilized with an intramolecular disulfide bridge suggests the existence of a new subclass of class IIb bacteriocins. IMPORTANCE Streptococcus gallolyticus subsp. gallolyticus (SGG), previously named Streptococcus bovis biotype I, is an opportunistic pathogen responsible for invasive infections (septicemia, endocarditis) in elderly people and is often associated with colon tumors. SGG is one of the first bacteria to be associated with the occurrence of colorectal cancer in humans. Previously, we showed that tumor-associated conditions in the colon provide SGG with an ideal environment to proliferate at the expense of phylogenetically and metabolically closely related commensal bacteria such as enterococci (1). SGG takes advantage of CRC-associated conditions to outcompete and substitute commensal members of the gut microbiota using a specific bacteriocin named gallocin, recently renamed gallocin A following the discovery of gallocin D in a peculiar SGG isolate. Here, we showed that gallocin A is a two-peptide bacteriocin and that both GllA1 and GllA2 peptides are required for antimicrobial activity. Gallocin A was shown to permeabilize bacterial membranes and kill phylogenetically closely related bacteria such as most streptococci, lactococci, and enterococci, probably through membrane pore formation. GllA1 and GllA2 secreted peptides are unusually long (42 and 60 amino acids long) and have very few charged amino acids compared to well-known class IIb bacteriocins. In silico modeling revealed that both GllA1 and GllA2 exhibit a similar hairpin-like conformation stabilized by an intramolecular disulfide bond. We also showed that the GIP immunity peptide forms a hairpin-like structure similar to GllA1/GllA2. Thus, we hypothesize that GIP blocks the formation of the GllA1/GllA2 complex by interacting with GllA1 or GllA2. Gallocin A may constitute the first class IIb bacteriocin which displays disulfide bridges important for its structure and activity and might be the founding member of a subtype of class IIb bacteriocins.

Emerging role of exosomes in vascular diseases.

Exosomes are biological small spherical lipid bilayer vesicles secreted by most cells in the body. Their contents include nucleic acids, proteins, and lipids. Exosomes can transfer material molecules between cells and consequently have a variety of biological functions, participating in disease development while exhibiting potential value as biomarkers and therapeutics. Growing evidence suggests that exosomes are vital mediators of vascular remodeling. Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), inflammatory cells, and adventitial fibroblasts (AFs) can communicate through exosomes; such communication is associated with inflammatory responses, cell migration and proliferation, and cell metabolism, leading to changes in vascular function and structure. Essential hypertension (EH), atherosclerosis (AS), and pulmonary arterial hypertension (PAH) are the most common vascular diseases and are associated with significant vascular remodeling. This paper reviews the latest research progress on the involvement of exosomes in vascular remodeling through intercellular information exchange and provides new ideas for understanding related diseases.

Investigation of the Impact of Lipid Acyl Chain Saturation on Fusion Peptide Interactions with Lipid Bilayers

The interaction of many peptides with lipid bilayer membranes strongly depends on the lipid composition. Here, a study of the impact of unsaturated lipid acyl chains on the interaction of a derivative of the HIV-1 fusion peptide with lipid bilayer vesicles is presented. Lipid bilayer vesicles composed of mixtures of lipids with two saturated acyl chains and lipids and one saturated and one unsaturated acyl chain, but identical head groups, were studied. The dependence of the peptide conformation on the unsaturated lipid content was probed by circular dichroism spectroscopy, while the impact of the peptide on the bilayer structure was determined by small-angle neutron scattering. The impact of the peptide on the lipid bilayer vesicle dynamics was investigated using neutron spin echo spectroscopy. Molecular dynamics simulations were used to characterize the behavior of the systems studied to determine if there were clear differences in their physical properties. The results reveal that the peptide–bilayer interaction is not a simple function of the unsaturated lipid acyl chain content of the bilayer. Instead, the peptide behavior is more consistent with that seen for the bilayer containing only unsaturated lipids, which is supported by lipid-specific interactions revealed by the simulations.

The Potential Roles of Exosomes Carrying APP and Tau Cleavage Products in Alzheimer’s Disease

Alzheimer's disease (AD) is the leading cause of dementia throughout the world. It is characterized by major amyloid plaques and neurofibrillary tangles (NFTs), which are composed of amyloid-β (Aβ) peptide and hyperphosphorylated Tau (p-Tau), respectively. Exosomes, which are secreted by cells, are single-membrane lipid bilayer vesicles found in bodily fluids and they have a diameter of 30-150 nm. Recently, they have been considered as critical carriers and biomarkers in AD, as they facilitate communication between cells and tissues by delivering proteins, lipids, and nucleic acids. This review demonstrates that exosomes are natural nanocontainers that carry APP as well as Tau cleavage products secreted by neuronal cells and that their formation is associated with the endosomal-lysosomal pathway. Moreover, these exosomes can transfer AD pathological molecules and participate in the pathophysiological process of AD; therefore, they have potential diagnostic and therapeutic value for AD and might also provide novel insights for screening and prevention of the disease.

Lipid-Specific Direct Translocation of the Cell-Penetrating Peptide NAF-144-67 across Bilayer Membranes.

The cell-penetrating peptide NAF-1 has recently emerged as a promising candidate for selective penetration and destruction of cancer cells. It displays numerous membrane-selective behaviors including cell-specific uptake and organelle-specific degradation. In this work, we explore membrane penetration and translocation of NAF-1 in model lipid bilayer vesicles as a function of lipid identity in zwitterionic phosphatidylcholine lipids mixed with anionic phosphatidylserine, phosphatidylglycerol, and phosphatidic acid lipids. By monitoring the digestion of NAF-1 using the protease trypsin located inside but not outside the vesicles, we determined that the translocation of NAF-1 was significantly enhanced by the presence of phosphatidic acid in the membrane compared to the other three anionic or zwitterionic lipids. These findings were correlated to fluorescence measurements of dansyl-labeled NAF-1, which revealed whether noncovalent interactions between NAF-1 and the bilayer were most stable either at the membrane/solution interface or within the membrane interior. Phosphatidic acid promoted interactions with fatty acid tails, while phosphatidylcholine, phosphatidylserine, and phosphatidylglycerol stabilized interactions with polar lipid headgroups. Interfacial vibrational sum frequency spectroscopy experiments revealed that the phosphate moiety on phosphatidic acid headgroups was better hydrated than on the other three lipids, which helped to shuttle NAF-1 into the hydrophobic region. Our findings demonstrate that permeation does not depend on the net charge on phospholipid lipid headgroups in these model vesicles and suggest a model wherein NAF-1 crosses membranes selectively due to lipid-specific interactions at bilayer surfaces.

Morphological Behavior of Liposomes and Lipid Nanoparticles.

Liposomes, which consist of bilayer lipids surrounding interior aqueous compartment(s), were first characterized nearly 60 years ago. Remarkably, many fundamental properties of liposomes and their micellar-like "solid core" counterparts (a lipid monolayer surrounding a hydrophobic core) and transitions between these structures remain poorly understood. In this work, we examine the effects of basic variables on the morphology adopted by lipid-based systems produced by rapid mixing of lipids in ethanol with aqueous media. We show that, for lipids such as distearolyphosphatidylcholine (DSPC)-cholesterol mixtures that form bilayer vesicles on hydration, osmotic stress can induce regions of high positive membrane curvature, leading to fusion between unilamellar vesicles to produce bilamellar vesicles. Addition of lyso PC, an "inverted cone"-shaped lipid that supports regions of high positive curvature, can inhibit the formation of these bilamellar vesicles by stabilizing a hemifused intermediate structure. Conversely, the presence of "cone"-shaped lipids such as dioleoylphosphatidylethanolamine (DOPE) that results in negative membrane curvature promotes fusion events subsequent to vesicle formation (during the ethanol dialysis stage), leading to bilamellar and multilamellar systems even in the absence of osmotic stress. Alternatively, the presence of increasing amounts of triolein, a lipid that is insoluble in lipid bilayers, results in increasing internal solid core structures until micellar-like systems with a hydrophobic core of triolein are achieved. These results are interpreted in terms of the intrinsic membrane curvature that bilayer vesicles can stably maintain as well as the ability of bilayer lipids to first form a monolayer around a solid core of hydrophobic material such as triolein and then, as the proportion of bilayer lipids is increased, progressively form bilayer structures that can eventually form a complete bilayer encapsulating both a hydrophobic core and an aqueous compartment. These hybrid intermediate structures may have utility as novel drug delivery systems.

Extracellular vesicles mediate biological information delivery: A double-edged sword in cardiac remodeling after myocardial infarction.

Acute myocardial infarction (AMI) is a severe ischemic disease with high morbidity and mortality worldwide. Maladaptive cardiac remodeling is a series of abnormalities in cardiac structure and function that occurs following myocardial infarction (MI). The pathophysiology of this process can be separated into two distinct phases: the initial inflammatory response, and the subsequent longer-term scar revision that includes the regression of inflammation, neovascularization, and fibrotic scar formation. Extracellular vesicles are nano-sized lipid bilayer vesicles released into the extracellular environment by eukaryotic cells, containing bioinformatic transmitters which are essential mediators of intercellular communication. EVs of different cellular origins play an essential role in cardiac remodeling after myocardial infarction. In this review, we first introduce the pathophysiology of post-infarction cardiac remodeling, as well as the biogenesis, classification, delivery, and functions of EVs. Then, we explore the dual role of these small molecule transmitters delivered by EVs in post-infarction cardiac remodeling, including the double-edged sword of pro-and anti-inflammation, and pro-and anti-fibrosis, which is significant for post-infarction cardiac repair. Finally, we discuss the pharmacological and engineered targeting of EVs for promoting heart repair after MI, thus revealing the potential value of targeted modulation of EVs and its use as a drug delivery vehicle in the therapeutic process of post-infarction cardiac remodeling.