201 results found
Barriga H, Ces O, Law R, et al., Engineering swollen cubosomes using cholesterol and anionic lipids, Langmuir: the ACS journal of surfaces and colloids, ISSN: 0743-7463
Dispersions of non-lamellar lipid membrane assemblies are gaining increasing interest for drug delivery and protein therapeutic application. A key bottleneck has been the lack of rational design rules for these systems linking different lipid species and conditions to defined lattice parameters and structures. We have developed robust methods to form cubosomes (nanoparticles with a porous internal structure) with water channel diameters of up to 171 Å which are over 4 times larger than archetypal cubosome structures. The water channel diameter can be tuned via the incorporation of cholesterol and the charged lipids DOPA, DOPG or DOPS. We have found that large molecules can be incorporated into the porous cubosome structure and these molecules can interact with the internal cubosome membrane. This offers huge potential for accessible encapsulation and protection of biomolecules, and development of confined interfacial reaction environments.
Tyler AII, Greenfield JL, Seddon JM, et al., 2019, Coupling Phase Behavior of Fatty Acid Containing Membranes to Membrane Bio-Mechanics, FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, Vol: 7, ISSN: 2296-634X
Mezzenga R, Seddon JM, Drummond CJ, et al., 2019, Nature-Inspired Design and Application of Lipidic Lyotropic Liquid Crystals., Adv Mater, Pages: e1900818-e1900818
Amphiphilic lipids aggregate in aqueous solution into a variety of structural arrangements. Among the plethora of ordered structures that have been reported, many have also been observed in nature. In addition, due to their unique morphologies, the hydrophilic and hydrophobic domains, very high internal interfacial surface area, and the multitude of possible order-order transitions depending on environmental changes, very promising applications have been developed for these systems in recent years. These include crystallization in inverse bicontinuous cubic phases for membrane protein structure determination, generation of advanced materials, sustained release of bioactive molecules, and control of chemical reactions. The outstanding diverse functionalities of lyotropic liquid crystalline phases found in nature and industry are closely related to the topology, including how their nanoscopic domains are organized. This leads to notable examples of correlation between structure and macroscopic properties, which is itself central to the performance of materials in general. The physical origin of the formation of the known classes of lipidic lyotropic liquid crystalline phases, their structure, and their occurrence in nature are described, and their application in materials science and engineering, biology, medical, and pharmaceutical products, and food science and technology are exemplified.
Devgan M, Seddon J, Brooks N, et al., 2019, The interaction of personal care formulations with skin mimetics, Joint 12th EBSA European Biophysics Congress / 10th IUPAP International Conference on Biological Physics (ICBP), Publisher: SPRINGER, Pages: S112-S112, ISSN: 0175-7571
Malia D, Seddon J, Law R, et al., 2019, The interaction of alpha-Tocopherol with model membranes, Joint 12th EBSA European Biophysics Congress / 10th IUPAP International Conference on Biological Physics (ICBP), Publisher: SPRINGER, Pages: S230-S230, ISSN: 0175-7571
Weatherby S, Seddon J, Vallance C, 2019, The 300(th) Faraday Discussion, FARADAY DISCUSSIONS, Vol: 214, Pages: 9-12, ISSN: 1359-6640
Khan H, Seddon JM, Law RV, et al., 2019, Effect of glycerol with sodium chloride on the Krafft point of sodium dodecyl sulfate using surface tension, JOURNAL OF COLLOID AND INTERFACE SCIENCE, Vol: 538, Pages: 75-82, ISSN: 0021-9797
Leivers M, Seddon JM, Declercq M, et al., 2019, Measurement of forces between supported cationic bilayers by colloid probe atomic force microscopy: electrolyte concentration and composition, Langmuir, Vol: 35, Pages: 729-738, ISSN: 0743-7463
The interactions between supported cationic surfactant bilayers were measured by colloidal probe atomic force spectroscopy and the effect of different halide salts was investigated. Di(alkyl iso-propyl ester) dimethyl ammonium methylsulfate (DIPEDMAMS) bilayers were fabricated by the vesicle fusion technique on muscovite mica. The interactions between the bilayers were measured in increasing concentrations of NaCl, NaBr, NaI and CaCl2. In NaCl the bilayer interactions were repulsive at all concentrations investigated, and the Debye length and surface potential were observed to decrease with increasing concentration. The interactions were found to follow the Electrical Double Layer (EDL) component of DLVO theory well. However Van der Waals forces were not detected, instead a strong hydration repulsion was observed at short separations. CaCl2 had a similar effect on the interactions as NaCl. NaBr and NaI were observed to be more efficient at decreasing the surface potential than the chloride salts, with the efficacy increasing with the ionic radius.
Tascini AS, Noro MG, Seddon JM, et al., 2019, Mechanisms of lipid extraction from skin lipid bilayers by sebum triglycerides, Physical Chemistry Chemical Physics, Vol: 21, Pages: 1471-1477, ISSN: 1463-9076
The skin surface, our first barrier against the external environment, is covered by the sebum oil, a lipid film composed of sebaceous and epidermal lipids, which is important in the regulation of the hydration level of our skin. Here, we investigate the pathways leading to the transfer of epidermal lipids from the skin lipid bilayer to the sebum. We show that the sebum triglycerides, a major component of sebum, interact strongly with the epidermal lipids and extract them from the bilayer. Using microsecond time scale molecular dynamics simulations, we identify and quantify the free energy associated with the skin lipid extraction process.
Tascini AS, Noro MG, Chen R, et al., 2018, Understanding the interactions between sebum triglycerides and water: a molecular dynamics simulation study., Physical Chemistry Chemical Physics, Vol: 20, Pages: 1848-1860, ISSN: 1463-9076
In recent years, sebum oil has been found to play a key role in the regulation of the hydration of the outermost layer of the skin, the stratum corneum. Understanding how a major component of the sebum oil, the triglyceride tri-cis-6-hexadecenoin (TG), interacts with water is an important step in gaining insight into the water regulation function of the sebum oil. Here we use molecular dynamics simulations to investigate the structural and interfacial properties of TG in bulk and at the air and water interface. Our model performs very well in reproducing experimental results, such as density, surface tensions and surface pressure area isotherms. We show that triglyceride molecules in the liquid phase assemble together, through the glycerol group, forming a single percolating network. TG-air interfaces orient the lipids with the interface enriched with the hydrophobic tails and the glycerol groups buried inside. When in contact with water, the TG molecules at the interface orient the glycerol group towards the water phase and adopt a characteristic trident conformation. Water is shown to penetrate the TG layer thanks to the interaction with the oxygen atoms of the TG molecules, which acts as a pathway for water diffusion. The activation energy for the passage of water is found to be ≈9.5kBT at 310 K, showing that the layer is permeable to water diffusion.
de Bruin A, Friddin MS, Elani Y, et al., 2017, A transparent 3D printed device for assembling droplet hydrogel bilayers (DHBs), RSC Advances, Vol: 7, Pages: 47796-47800, ISSN: 2046-2069
We report a new approach for assembling droplet hydrogel bilayers (DHBs) using a transparent 3D printed device. We characterise the transparency of our platform, confirm bilayer formation using electrical measurements and show that single-channel recordings can be obtained using our reusable rapid prototyped device. This method significantly reduces the cost and infrastructure required to develop devices for DHB assembly and downstream study.
Richens JL, Tyler AII, Barriga HMG, et al., 2017, Spontaneous charged lipid transfer between lipid vesicles, Scientific Reports, Vol: 7, ISSN: 2045-2322
An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are uorescentlylabelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE).Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting ina uorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a rst-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodi ed lipids, continuous monitoring of transfer and simpli ed experimental procedures.
Kluzek M, Tyler AII, Wang S, et al., 2017, Influence of a pH-sensitive polymer on the structure of monoolein cubosomes, Soft Matter, Vol: 13, Pages: 7571-7577, ISSN: 1744-683X
Cubosomes consist in submicron size particles of lipid bicontinuous cubic phases stabilized by surfactant polymers. They provide an appealing road towards the practical use of lipid cubic phases for pharmaceutical and cosmetic applications, and efforts are currently being made to control the encapsulation and release properties of these colloidal objects. We overcome in this work the lack of sensitivity of monoolein cubosomes to pH conditions by using a pH sensitive polymer designed to strongly interact with the lipid structure at low pH. Our cryo-transmission electron microscope (cryo-TEM) and small-angle X-ray scattering (SAXS) results show that in the presence of the polymer the cubic phase structure is preserved at neutral pH, albeit with a larger cell size. At pH 5.5, in the presence of the polymer, the nanostructure of the cubosome particles is significantly altered, providing a pathway to design pH-responsive cubosomes for applications in drug delivery.
Tascini AS, Chen R, Seddon JM, et al., 2017, How wettable is the skin surface?, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S232-S232, ISSN: 0175-7571
Barriga HM, Ces O, Law RV, et al., 2017, Model membrane systems for protein therapeutics, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S117-S117, ISSN: 0175-7571
Gainar A, Tyler AII, Brooks NJ, et al., 2017, Understanding the lyotropic phase behaviour of cytochrome-c incorporated in monoolein mesophases, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S120-S120, ISSN: 0175-7571
Trantidou T, Friddin M, Elani Y, et al., 2017, Engineering compartmentalized biomimetic micro- and nanocontainers, ACS Nano, Vol: 11, Pages: 6549-6565, ISSN: 1936-086X
Compartmentalization of biological content and function is a key architectural feature in biology, where membrane bound micro- and nanocompartments are used for performing a host of highly specialized and tightly regulated biological functions. The benefit of compartmentalization as a design principle is behind its ubiquity in cells and has led to it being a central engineering theme in construction of artificial cell-like systems. In this review, we discuss the attractions of designing compartmentalized membrane-bound constructs and review a range of biomimetic membrane architectures that span length scales, focusing on lipid-based structures but also addressing polymer-based and hybrid approaches. These include nested vesicles, multicompartment vesicles, large-scale vesicle networks, as well as droplet interface bilayers, and double-emulsion multiphase systems (multisomes). We outline key examples of how such structures have been functionalized with biological and synthetic machinery, for example, to manufacture and deliver drugs and metabolic compounds, to replicate intracellular signaling cascades, and to demonstrate collective behaviors as minimal tissue constructs. Particular emphasis is placed on the applications of these architectures and the state-of-the-art microfluidic engineering required to fabricate, functionalize, and precisely assemble them. Finally, we outline the future directions of these technologies and highlight how they could be applied to engineer the next generation of cell models, therapeutic agents, and microreactors, together with the diverse applications in the emerging field of bottom-up synthetic biology.
Boyd C, Parsons ES, Smith RAG, et al., 2016, Disentangling the roles of cholesterol and CD59 in intermedilysin pore formation, Scientific Reports, Vol: 6, ISSN: 2045-2322
The plasma membrane provides an essential barrier, shielding a cell from the pressures of its external environment. Pore-forming proteins, deployed by both hosts and pathogens alike, breach this barrier to lyse target cells. Intermedilysin is a cholesterol-dependent cytolysin that requires the human immune receptor CD59, in addition to cholesterol, to form giant β-barrel pores in host membranes. Here we integrate biochemical assays with electron microscopy and atomic force microscopy to distinguish the roles of these two receptors in mediating structural transitions of pore formation. CD59 is required for the specific coordination of intermedilysin (ILY) monomers and for triggering collapse of an oligomeric prepore. Movement of Domain 2 with respect to Domain 3 of ILY is essential for forming a late prepore intermediate that releases CD59, while the role of cholesterol may be limited to insertion of the transmembrane segments. Together these data define a structural timeline for ILY pore formation and suggest a mechanism that is relevant to understanding other pore-forming toxins that also require CD59.
Chan CL, Bolognesi G, Bhandarkar A, et al., 2016, DROPLAY: laser writing of functional patterns within biological microdroplet displays, Lab on a Chip, Vol: 16, Pages: 4621-4627, ISSN: 1473-0197
In this study, we introduce an optofluidic method for the rapid construction of large-area cell-sized droplet assemblieswith user-defined re-writable two-dimensional patterns of functional droplets. Light responsive water-in-oil dropletscapable of releasing fluorescent dye molecules upon exposure were generated and self-assembled into arrays in amicrofluidic device. This biological architecture was exploited by the scanning laser of a confocal microscope to ‘write’ userdefined patterns of differentiated (fluorescent) droplets in a network of originally undifferentiated (non-fluorescent)droplets. As a result, long lasting images were produced on a droplet fabric with droplets acting as pixels of a biologicalmonitor, which can be erased and re-written on-demand. Regio-specific light-induced droplet differentiation within a largepopulation of droplets provides a new paradigm for the rapid construction of bio-synthetic systems with potential as tissuemimics and biological display materials.
Friddin MS, Bolognesi G, Elani Y, et al., 2016, Optically assembled droplet interface bilayer (OptiDIB) networks from cell-sized microdroplets, Soft Matter, Vol: 12, Pages: 7731-7734, ISSN: 1744-6848
We report a new platform technology to systematically assemble droplet interface bilayer (DIB) networks in user-defined 3D architectures from cell-sized droplets using optical tweezers. Our OptiDIB platform is the first demonstration of optical trapping to precisely construct 3D DIB networks, paving the way for the development of a new generation of modular bio-systems.
Friddin MS, Bolognesi G, Elani Y, et al., The optical assembly of bilayer networks from cell-sized droplets for synthetic biology, Systems and Synthetic Biology
Brooks NJ, Cates ME, Clegg PS, et al., 2016, Soft Interfacial Materials: from Fundamentals to Formulation, Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, Vol: 374, ISSN: 1364-503X
This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.The science of soft interfaces (lipid membranes, emulsions, particle-stabilized droplets, etc.) is rapidly moving into an era of predictive capability that allows the design and development of advanced materials to be based on secure scientific knowledge. This Theme Issue reports papers presented at a Discussion Meeting intended not only to address the fundamental science, focusing on generic design principles for self-organization and interfacial structure, but also to explore the resulting prospects for ‘informed formulation’ of new and improved industrial products.At the end of this introductory essay, we briefly summarize some of the scientific progress reported in the individual research and review papers included in this volume. Before doing so, we take the opportunity to describe some of the background thinking that shaped the content and aims of the Meeting as conceived by the organizers.This essay is intended to be thought provoking, not definitive; much of it is based on a wrap-up discussion that two of us (Alex Lips and Wilson Poon) contributed at the end of the Meeting itself. In it, we focus on the relationship between science (‘fundamentals’) and technology (‘formulation’). At least in the soft materials area, this represents a subtler and more interesting form of symbiosis than is often assumed.
Friddin MS, Bolognesi G, Elani Y, et al., Optical tweezers to assemble 2D and 3D droplet interface bilayer networks from cell-sized droplets, EMBL Microfluidics
Karamdad K, Law R, Seddon J, et al., 2016, Studying the effects of asymmetry on the bending rigidity of lipid membranes formed by microfluidics, Chemical Communications (London), Vol: 52, Pages: 5277-5280, ISSN: 0009-241X
In this article we detail a robust high-throughput microfluidic platform capable of fabricating either symmetric or asymmetric giant unilamellar vesicles (GUVs) and characterise the mechanical properties of their membranes.
Zhang Y, Carter JW, Lervik A, et al., 2016, Structural organization of sterol molecules in DPPC bilayers: a coarse-grained molecular dynamics investigation, Soft Matter, Vol: 12, Pages: 2108-2117, ISSN: 1744-6848
Martin HP, Brooks NJ, Seddon JM, et al., 2016, Microfluidic processing of concentrated surfactant mixtures: online SAXS, microscopy and rheology, Soft Matter, Vol: 12, Pages: 1750-1758, ISSN: 1744-6848
Friddin MS, Bolognesi G, Elani Y, et al., 2016, Light-driven drag and drop assembly of micron-scale bilayer networks for synthetic biology, Pages: 545-546
We have developed a new method to assemble single- or multi-layered networks of droplet interface bilayers (DIBs) from cell-sized droplets using a single beam optical trap (optical tweezers). The novelty of our approach is the ability to directly trap the microdroplets with the laser and manipulate them in 3D to construct DIB networks of user-defined architectures. Our method does not require a complex optical setup, is versatile, contactless, benefits from both high spatial and temporal resolution, and could set a new paradigm for the assembly of smart, synthetic biosystems.
Ces O, Elani Y, Karamdad K, et al., 2016, Novel microfluidic technologies for the bottom-up construction of artificial cells
© 2016 Institution of Engineering and Technology. All rights reserved. This talk will outline novel microfluidic strategies for biomembrane engineering that are capable of fabricating vesicles , droplet interface bilayer networks , multisomes  and artificial tissues  where parameters such as membrane asymmetry, membrane curvature, compartment connectivity and individual compartment contents can be controlled. Various bulk methods, such as extrusion, gentle hydration and electroformation, have been synonymous with the formation of lipid vesicles over recent years. However these strategies suffer from significant shortcomings associated with these processes including limited control of vesicle structural parameters such as size, lamellarity, membrane composition and internal contents. To address this technological bottleneck we have developed novel microfluidic platforms to form lipid vesicles in high-Throughput with full control over the composition of both the inner and outer leaflet of the membrane thereby enabling the manufacture of symmetric and asymmetric vesicles. This is achieved by manufacturing microfluidic channels with a step junction, produced by double-layer photolithography, which facilitates the transfer of a W/O emulsion across an oil-water phase boundary and the self-Assembly of a phospholipid bilayer. These platforms are being used to explore the role of asymmetry in biological systems  and study the engineering rules that regulate membrane mediated protein-protein interactions . In addition, these technologies are enabling the construction of biological machines capable of acting as micro-reactors , environmental sensors and smart delivery vehicles  as well as complex multi-compartment artificial cells where the contents and connectivity of each compartment can be controlled. These compartments are separated by biological functional membranes that can facilitate transport between the compartments themselves and between
Carreras P, Elani Y, Law RV, et al., 2015, A microfluidic platform for size-dependent generation of droplet interface bilayer networks on rails, Biomicrofluidics, Vol: 9, ISSN: 1932-1058
Dropletinterface bilayer (DIB) networks are emerging as a cornerstone technology for the bottom up construction of cell-like and tissue-like structures and bio-devices. They are an exciting and versatile model-membrane platform, seeing increasing use in the disciplines of synthetic biology, chemical biology, and membrane biophysics. DIBs are formed when lipid-coated water-in-oil droplets are brought together—oil is excluded from the interface, resulting in a bilayer. Perhaps the greatest feature of the DIB platform is the ability to generate bilayer networks by connecting multiple droplets together, which can in turn be used in applications ranging from tissue mimics, multicellular models, and bio-devices. For such applications, the construction and release of DIB networks of defined size and composition on-demand is crucial. We have developed a droplet-based microfluidic method for the generation of different sized DIB networks (300–1500 pl droplets) on-chip. We do this by employing a droplet-on-rails strategy where droplets are guided down designated paths of a chip with the aid of microfabricated grooves or “rails,” and droplets of set sizes are selectively directed to specific rails using auxiliary flows. In this way we can uniquely produce parallel bilayer networks of defined sizes. By trapping several droplets in a rail, extended DIB networks containing up to 20 sequential bilayers could be constructed. The trapped DIB arrays can be composed of different lipid types and can be released on-demand and regenerated within seconds. We show that chemical signals can be propagated across the bio-network by transplanting enzymatic reaction cascades for inter-droplet communication.
Barriga HMG, Law RV, Seddon JM, et al., 2015, The effect of hydrostatic pressure on model membrane domain composition and lateral compressibility, Physical Chemistry Chemical Physics, ISSN: 1463-9084
Phase separation in ternary model membranes is known to occur over a range of temperatures and compositions and can be induced by increasing hydrostatic pressure. We have used small angle X-ray scattering (SAXS) to study phase separation along pre-determined tie lines in dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC) and cholesterol (CHOL) mixtures. We can unequivocally distinguish the liquid ordered (Lo) and liquid disordered (Ld) phases in diffraction patterns from biphasic mixtures and compare their lateral compressibility. The variation of tie line endpoints with increasing hydrostatic pressure was determined, at atmospheric pressure and up to 100 MPa. We find an extension and shift of the tie lines towards the DOPC rich region of the phase diagram at increased pressure, this behaviour differs slightly from that reported for decreasing temperature.
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