Faraday Discussions最新文献

{"title":"Near-infrared responsive three-component supramolecular hydrogels of peptide, agarose and upconversion nanoparticles.","authors":"Ivo Rosenbusch, Dominik Mählmann, Bart Jan Ravoo","doi":"10.1039/d4fd00203b","DOIUrl":"https://doi.org/10.1039/d4fd00203b","url":null,"abstract":"<p><p>Self-assembled, low molecular weight hydrogels are of particular interest for the development of responsive materials because they exhibit tunable viscoelasticity, high water content, and shear-thinning behavior, which make them suitable for various applications as biomimetic materials. Moreover, such hydrogels are quite easy to prepare. Here, a three-component gel is prepared by adding the peptide AAP-FGDS to an agarose polymer network. The photoresponsive peptide hydrogel exhibits excellent reversible properties. The photoisomerization of the peptide is enabled by lanthanide-doped upconversion nanoparticles (UCNP) added as a third component in the gel. UCNP can convert excitation in the near infrared (NIR) range into emission of higher energy through the process of upconversion. Irradiation with an NIR laser dissolves the self-assembled three-dimensional network structure of the peptide, resulting in a softer hydrogel. The three-component supramolecular gel can potentially be used for <i>in vivo</i> applications considering the fact that (unlike harmful UV light) NIR light can penetrate deeply into tissue.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusion of asymmetric membranes: the emergence of a preferred direction.","authors":"Petr Shendrik, Raya Sorkin, Gonen Golani","doi":"10.1039/d4fd00189c","DOIUrl":"https://doi.org/10.1039/d4fd00189c","url":null,"abstract":"<p><p>The fusion of lipid membranes progresses through a series of intermediate steps with two significant energy barriers: hemifusion-stalk formation and fusion-pore expansion. The cell's ability to tune these energy barriers is crucial as they determine the rate of many biological processes involving membrane fusion. However, a mechanism that allows the cell to manipulate both barriers in the same direction remains elusive, since membrane properties that the cell could dynamically tune during its life cycle, such as the lipids' spontaneous curvatures and membrane tension, have an opposite effect on the two barriers: tension inhibits stalk formation while promoting fusion-pore expansion. In contrast, increasing the total membrane concentration of lipids with negative intrinsic curvatures, such as cholesterol, promotes hemifusion-stalk formation while inhibiting pore expansion, and <i>vice versa</i> for lipids with positive intrinsic curvatures. Therefore, changes in these membrane properties increase one energy barrier at the expense of the other, resulting in a mixed effect on the fusion reaction. A possible mechanism to change both barriers in the same direction is by inducing lipid composition asymmetry, which results in tension and spontaneous curvature differences between the monolayers. To test the feasibility of this mechanism, a continuum elastic model was used to simulate the fusion intermediates and calculate the changes in the energy barriers. The calculations showed that a reasonable lipid composition asymmetry could lead to a 10-20<i>k</i>_B<i>T</i> difference in both energy barriers, depending on the direction from which fusion occurs. We further provide experimental support to the model predictions, demonstrating changes in the time to hemifusion upon asymmetry introduction. These results indicate that biological membranes, which are asymmetric, have a preferred direction for fusion.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay of composition and mechanics in the thermodynamics of asymmetric ternary lipid membranes.","authors":"Malavika Varma, Markus Deserno","doi":"10.1039/d4fd00196f","DOIUrl":"https://doi.org/10.1039/d4fd00196f","url":null,"abstract":"<p><p>Eukaryotic lipid membranes are both compositionally complex and strongly asymmetric. Preferential lipid interactions enable coexistence between two fluid phases and an associated critical point, while bilayer asymmetry leads to leaflet-specific values for many observables-most saliently composition, but also a difference in leaflet tensions, for which we introduced the term \"differential stress.\" Lipid mixing thermodynamics has been extensively studied, notably in idealized ternary model systems, and interest in asymmetry has grown significantly in the past decade, but their interplay remains poorly understood. Here we propose a conceptual framework for the thermodynamics of asymmetric ternary lipid membranes. Cholesterol emerges as an essential actor playing two different roles: first, it controls lipid mixing; second, it couples the compositional phase points of the two leaflets by achieving chemical equilibrium between them. Since differential stress can squeeze cholesterol from one leaflet into the other, this couples mechanical properties such as lateral stresses and curvature torques directly to mixing thermodynamics. Using coarse-grained simulations, we explore implications for leaflet coexistence, mechanical stability of giant vesicles, and differential stress driven phase segregation in a single leaflet. We hope this framework enables a fresh look at some persistent puzzles in this field, most notably the elusive nature of lipid rafts.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does plasma membrane transbilayer asymmetry coupled to lipid nanodomains drive fast kinetics of FGF2 membrane translocation into the extracellular space?","authors":"Fabio Lolicato, Manpreet Kaur, Ana Marija Knez, Roberto Saleppico, Walter Nickel","doi":"10.1039/d4fd00208c","DOIUrl":"https://doi.org/10.1039/d4fd00208c","url":null,"abstract":"<p><p>Fibroblast Growth Factor 2 (FGF2) is a potent mitogen secreted from mammalian cells through an unconventional secretory pathway. This process is mediated by direct translocation of FGF2 across the plasma membrane into the extracellular space. It requires several components that are asymmetrically distributed between the two leaflets of the plasma membrane. At the inner plasma membrane leaflet, FGF2 undergoes sequential interactions with the Na,K-ATPase, Tec kinase, and the phosphoinositide PI(4,5)P₂. While the Na,K-ATPase, and Tec kinase are auxiliary factors, interactions of FGF2 with PI(4,5)P₂ trigger the core mechanism of FGF2 membrane translocation, inducing FGF2-oligomerization-dependent formation of lipidic membrane pores. At the outer plasma membrane leaflet, membrane-inserted FGF2 oligomers are captured and disassembled by Glypican-1 (GPC1), resulting in translocation of FGF2 to the cell surface. In a cellular context, a single FGF2 membrane translocation event occurs within 200 milliseconds. In contrast, in an <i>in vitro</i> system, which uses a fully reconstituted liposomal inside-out system with FGF2 added from the outside and luminal encapsulation of high-affinity heparin molecules, FGF2 membrane translocation takes several minutes. Here, we hypothesize that the observed difference is, at least in part, due to the asymmetrical membrane lipid distribution and the spatial organization of the FGF2 translocation machinery in native plasma membranes. We suggest that the molecular machinery mediating FGF2 membrane translocation assembles in ordered nanodomains, characterized by sphingomyelin (SM), cholesterol and phosphoinositide PI(4,5)P₂ coupled together. The transbilayer asymmetry of these lipids likely plays a crucial role in regulating the thermodynamics and kinetics of FGF2-induced membrane pore formation. Therefore, succeeding in reconstituting the FGF2 translocation machinery in artificial membranes with an asymmetric transbilayer distribution of SM, PI(4,5)P₂ and other membrane lipids may reveal a direct impact on pore-opening kinetics. Similarly, disrupting lipid asymmetry in cells may significantly impact FGF2 secretion rates, a finding that would underscore the importance of the spatial organization of lipids in membrane dynamics. Testing this hypothesis may advance our understanding of how membrane asymmetry and ordered lipid nanodomains regulate critical biological processes, such as the unconventional secretion of FGF2.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surfactant-like peptide gels are based on cross-β amyloid fibrils.","authors":"Abhinaba Das, Ordy Gnewou, Xiaobing Zuo, Fengbin Wang, Vincent P Conticello","doi":"10.1039/d4fd00190g","DOIUrl":"10.1039/d4fd00190g","url":null,"abstract":"<p><p>Surfactant-like peptides, in which hydrophilic and hydrophobic residues are encoded within different domains in the peptide sequence, undergo facile self-assembly in aqueous solution to form supramolecular hydrogels. These peptides have been explored extensively as substrates for the creation of functional materials since a wide variety of amphipathic sequences can be prepared from commonly available amino acid precursors. The self-assembly behavior of surfactant-like peptides has been compared to that observed for small molecule amphiphiles in which nanoscale phase separation of the hydrophobic domains drives the self-assembly of supramolecular structures. Here, we investigate the relationship between sequence and supramolecular structure for a pair of bola-amphiphilic peptides, Ac-KLIIIK-NH₂ (L2) and Ac-KIIILK-NH₂ (L5). Despite similar length, composition, and polar sequence pattern, L2 and L5 form morphologically distinct assemblies, nanosheets and nanotubes, respectively. Cryo-EM helical reconstruction was employed to determine the structure of the L5 nanotube at near-atomic resolution. Rather than displaying self-assembly behavior analogous to conventional amphiphiles, the packing arrangement of peptides in the L5 nanotube displayed steric zipper interfaces that resembled those observed in the structures of β-amyloid fibrils. Like amyloids, the supramolecular structures of the L2 and L5 assemblies were sensitive to conservative amino acid substitutions within an otherwise identical amphipathic sequence pattern. This study highlights the need to better understand the relationship between sequence and supramolecular structure to facilitate the development of functional peptide-based materials for biomaterials applications.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of peptide chirality on their protein-triggered supramolecular hydrogelation.","authors":"Shahaji H More, Tetiana Dorosh, Jean-Yves Runser, Alexis Bigo-Simon, Rachel Schurhammer, Vincent Ball, Leandro Jacomine, Marc Schmutz, Alain Chaumont, Pierre Schaaf, Loïc Jierry","doi":"10.1039/d5fd00007f","DOIUrl":"https://doi.org/10.1039/d5fd00007f","url":null,"abstract":"<p><p>Many articles describe the use of enzymes to induce the formation of a supramolecular hydrogel. These enzymes catalyze the transformation of water-soluble precursors, often short peptides, into hydrogelators. The use of non-enzymatic proteins to induce or stabilize peptide self-assembly is a rarely reported phenomenon, which raises fundamental questions: how can a protein induce peptide self-assembly? How is the peptide recognized and how does it, or the peptide assembly, interact with the protein? The heptapeptide Fmoc-GFFYE-NH-(CH₂)₂-<i>s-s</i>-(CH₂)₂-NH-CO-(CH₂)₂-CO-EE-OH, called L-1 (L = natural chiral amino acids), is a water-soluble compound leading to an increasingly viscous solution over time due to the formation of nanofibers, but does not result in hydrogel (at least not within 3 months). When bovine serum albumin (BSA) is added to a freshly prepared solution of L-1, a hydrogel is obtained in less than 10 min. The variation in the L-1/BSA ratio has an impact on the gelation rate and the mechanical properties of the resulting hydrogel. Thus, the protein appears to act as (i) a catalyst and (ii) a cross-linking point. Strikingly, if the enantiomer D-1 (D = unnatural chiral amino acids) is used instead of L-1, the mixture with BSA remains liquid and non-viscous. Similar behavior is also observed for other proteins. Spectroscopic analyses (CD, fluorescence) and electronic microscopy images confirm that the L-1 peptide self-assembles in nanofibers of 10 nm diameter through β-sheet organization, which is not the case for the peptide D-1. A molecular dynamics study shows that BSA is capable of interacting with both enantiomer peptides L-1 and D-1. However, interaction with L-1 tends to unfold the peptide backbone, making the interaction with the protein more stable and promoting the assembly of L-1 peptides. Conversely, the interaction between BSA and D-1 is more dynamic and appears to be less spatially localized on the BSA. Furthermore, in this interaction, the D-1 peptide keeps its globular conformation. These results highlight the impact of a short peptide's chirality on protein-triggered supramolecular hydrogelation.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytantriol and monoolein in aqueous deep eutectic solvent and protic ionic liquid solutions.","authors":"Karen J Edler, Gregory G Warr, Alexander M Djerdjev, Minh Thu Lam, Adrian M Hawley, Stephen Mudie","doi":"10.1039/d5fd00004a","DOIUrl":"https://doi.org/10.1039/d5fd00004a","url":null,"abstract":"<p><p>Lyotropic liquid crystal gels of phytantriol and monoolein are well known examples of self-assembled systems in water, which have multiple applications across biomedical and materials science. However aqueous systems can be restricted by rapid solvent evaporation, and the limited solubility of some species in water. Here we explore the formation of liquid crystalline phases of phytantriol and monoolein in mixtures of water with two protic ionic liquids, ethylammonium nitrate (EAN) and ethanolammonium nitrate (EtAN), and three deep eutectic solvents (DES) formed from mixtures of choline chloride with urea, fructose or citric acid. The structures of the gel phase in excess solvent were measured using small angle X-ray scattering for a fixed lipid concentration (5% w/w) as a function of temperature. The phase diagrams of both lipids in DES-water mixtures and the non-amphiphilic ionic liquid, EtAN, indicate that higher negative curvature inverse hexagonal structures are favoured by addition of water. However, the amphiphilic ionic liquid EAN swells and stabilises the cubic <i>Pn</i>3<i>m</i> structure. The interplay of solvent structure, polarity and molecular size are key to understanding the formation and stability of lyotropic liquid crystalline gels in these systems.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated descriptors for high-throughput screening of peptide self-assembly.","authors":"Raj Kumar Rajaram Baskaran, Alexander van Teijlingen, Tell Tuttle","doi":"10.1039/d4fd00201f","DOIUrl":"https://doi.org/10.1039/d4fd00201f","url":null,"abstract":"<p><p>We present five automated descriptors: Aggregate Detection Index (ADI); Sheet Formation Index (SFI); Vesicle Formation Index (VFI); Tube Formation Index (TFI); and Fibre Formation Index (FFI), that have been designed for analysing peptide self-assembly in molecular dynamics simulations. These descriptors, implemented as Python modules, enhance analytical precision and enable the development of screening methods tailored to specific structural targets rather than general aggregation. Initially tested on the FF dipeptide, the descriptors were validated using a comprehensive dipeptide dataset. This approach facilitates the identification of promising self-assembling moieties with nanoscale properties directly linked to macroscale functions, such as hydrogel formation.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of counterion and salt form on the properties of long-acting injectable peptide hydrogels for drug delivery.","authors":"Jessica V Moore, Emily R Cross, Yuming An, Sreekanth Pentlavalli, Sophie M Coulter, Han Sun, Garry Laverty","doi":"10.1039/d4fd00194j","DOIUrl":"10.1039/d4fd00194j","url":null,"abstract":"<p><p>Modifying the salt form of active pharmaceutical ingredients is a common method to enhance their physicochemical and biological properties, whilst improving their ability to be formulated into medicines that can be effectively delivered to patients. Salts and counterions are especially relevant to peptide therapies, given that the majority of low molecular weight peptides synthesised by solid-phase protocols form a trifluoroacetate (TFA) salt due to the use of trifluoroacetic acid in resin cleaving and follow-on purification methods. TFA salts are not viewed as favourably by medicine regulators and can be defined as a new chemical entity entirely due to their different biological and physicochemical properties. Despite some exceptions, the vast majority of therapeutic peptides are marketed as hydrochloride (HCl) or acetate salts, even though most early research and development is centred on TFA salts. The aim of the study was to compare the impact of salt form (TFA <i>vs.</i> HCl) on the biostability, cell cytotoxicity, drug release and rheological properties of a Napffky(p)G-OH peptide hydrogel platform that demonstrates promise as a long-acting drug delivery system. This study demonstrated no significant difference between the salt forms for properties important to its intended use. This paper also raises important points for discussion relating to the environmental and regulatory status of peptide salts and their use as pharmaceuticals.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programming two-component peptide self-assembly by tuning the hydrophobic linker.","authors":"Sangshuang Li, Huayang Liu, Yu Fang, Yaoting Li, Laicheng Zhou, Dinghao Chen, Juan Liang, Huaimin Wang","doi":"10.1039/d4fd00209a","DOIUrl":"https://doi.org/10.1039/d4fd00209a","url":null,"abstract":"<p><p>Molecular self-assembly enables the formation of intricate networks through non-covalent interactions, serving as a key strategy for constructing structures ranging from molecules to macroscopic forms. While zero-dimensional and one-dimensional nanostructures have been widely achieved, two-dimensional nanostrip structures present unique advantages in biomedical and other applications due to their high surface area and potential for functionalization. However, their efficient design and precise regulation remain challenging. This study systematically explores how different hydrophobic amino acid linkers impact the microscopic morphology in two-component co-assembly systems with strong electrostatic interactions. The introduction of the AA linker resulted in distinctive 2D nanostrips, which stacked to form bilayer sheets, whereas VV, LL, and NleNle linkers formed one-dimensional fibers. In contrast, GG and PP linkers did not produce stable aggregates. Our findings highlight the role of intermolecular interactions in the development of 2D assemblies, providing new insights into the design and application of 2D materials.</p>","PeriodicalId":76,"journal":{"name":"Faraday Discussions","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}