Publications
220 results found
Saurabh S, Zhang Q, Seddon JM, et al., 2024, Unraveling the microscopic mechanism of molecular ion interaction with monoclonal antibodies: impact on protein aggregation, Molecular Pharmaceutics, Vol: 21, Pages: 1285-1299, ISSN: 1543-8384
Understanding and predicting protein aggregation represents one of the major challenges in accelerating the pharmaceutical development of protein therapeutics. In addition to maintaining the solution pH, buffers influence both monoclonal antibody (mAb) aggregation in solution and the aggregation mechanisms since the latter depend on the protein charge. Molecular-level insight is necessary to understand the relationship between the buffer-mAb interaction and mAb aggregation. Here, we use all-atom molecular dynamics simulations to investigate the interaction of phosphate (Phos) and citrate (Cit) buffer ions with the Fab and Fc domains of mAb COE3. We demonstrate that Phos and Cit ions feature binding mechanisms, with the protein that are very different from those reported previously for histidine (His). These differences are reflected in distinctive ion-protein binding modes and adsorption/desorption kinetics of the buffer molecules from the mAb surface and result in dissimilar effects of these buffer species on mAb aggregation. While His shows significant affinity toward hydrophobic amino acids on the protein surface, Phos and Cit ions preferentially bind to charged amino acids. We also show that Phos and Cit anions provide bridging contacts between basic amino acids in neighboring proteins. The implications of such contacts and their connection to mAb aggregation in therapeutic formulations are discussed.
Saurabh S, Zhang Q, Li Z, et al., 2024, Mechanistic insights into the adsorption of monoclonal antibodies at the water/vapor interface, Molecular Pharmaceutics, Vol: 21, Pages: 704-717, ISSN: 1543-8384
Monoclonal antibodies (mAbs) are active components of therapeutic formulations that interact with the water-vapor interface during manufacturing, storage, and administration. Surface adsorption has been demonstrated to mediate antibody aggregation, which leads to a loss of therapeutic efficacy. Controlling mAb adsorption at interfaces requires a deep understanding of the microscopic processes that lead to adsorption and identification of the protein regions that drive mAb surface activity. Here, we report all-atom molecular dynamics (MD) simulations of the adsorption behavior of a full IgG1-type antibody at the water/vapor interface. We demonstrate that small local changes in the protein structure play a crucial role in promoting adsorption. Also, interfacial adsorption triggers structural changes in the antibody, potentially contributing to the further enhancement of surface activity. Moreover, we identify key amino acid sequences that determine the adsorption of antibodies at the water-air interface and outline strategies to control the surface activity of these important therapeutic proteins.
Elani Y, Seddon J, 2023, What it means to be alive: a synthetic cell perspective, Interface Focus, Vol: 13, Pages: 1-3, ISSN: 2042-8898
Advances in bottom-up synthetic biology offer the exciting—albeit contentious—prospect of transitioning bio-science researchers from passive observers of life to potential creators of it. Synthetic cells closely emulate the attributes of their biological counterparts. These rationally designed microsystems exhibit emergent properties and life-like functionalities. They can therefore be used as simplified cell models to decipher the rules of life, and as programmable biologically powered micromachines for application in healthcare and biotechnology more broadly. While there is a consensus that current synthetic cells are not yet ‘living’, the question of what defines ‘aliveness’ is gaining increasing relevance. Exploring this concept necessitates a multidisciplinary approach, where scientists from across domains in the physical, life, engineering and social sciences participate in community-level discussions, together with the acceptance of a set of criteria which defines a living system. Achieving a widely accepted definition of ‘living’ represents a possible mission-oriented endpoint to the synthetic cell endeavour, uniting the community towards a common goal. As the field evolves, researchers must address regulatory, ethical, societal and public perception implications, while fostering collaborative efforts to harness the transformative potential of synthetic cells.
Saurabh S, Li Z, Hollowell P, et al., 2023, Structure and interaction of therapeutic proteins in solution: a combined simulation and experimental study, Molecular Physics: An International Journal at the Interface Between Chemistry and Physics, Vol: 121, Pages: 1-16, ISSN: 0026-8976
The aggregation of therapeutic proteins in solution has attracted significant interest, driving efforts to understand the relationship between microscopic structural changes and protein-protein interactions determining aggregation processes in solution. Additionally, there is substantial interest in being able to predict aggregation based on protein structure as part of molecular developability assessments. Molecular Dynamics provides theoretical tools to complement experimental studies and to interrogate and identify the microscopic mechanisms determining aggregation. Here we perform all-atom MD simulations to study the structure and inter-protein interaction of the Fab and Fc fragments of the monoclonal antibody (mAb) COE3. We unravel the role of ion-protein interactions in building the ionic double layer and determining effective inter-protein interaction. Further, we demonstrate, using various state-of-the-art force fields (charmm, gromos, amber, opls/aa), that the protein solvation, ionic structure and protein-protein interaction depend significantly on the force field parameters. We perform SANS and Static Light Scattering experiments to assess the accuracy of the different forcefields. Comparison of the simulated and experimental results reveal significant differences in the forcefields' performance, particularly in their ability to predict the protein size in solution and inter-protein interactions quantified through the second virial coefficients. In addition, the performance of the forcefields is correlated with the protein hydration structure.
Pilkington C, Contini C, Barritt J, et al., 2023, A microfluidic platform for the controlled synthesis of architecturally complex liquid crystalline nanoparticles, Scientific Reports, Vol: 13, Pages: 1-14, ISSN: 2045-2322
Soft-matter nanoparticles are of great interest for their applications in biotechnology, therapeutic delivery, and in vivo imaging. Underpinningthis is their biocompatibility, potential for selective targeting, attractive pharmacokinetic properties, and amenability to downstreamfunctionalisation. Morphological diversity inherent to soft-matter particles can give rise to enhanced functionality. However, this diversityremains untapped in clinical and industrial settings, and only the simplest of particle architectures (spherical lipid vesicles and lipid/polymernanoparticles (LNPs)) have been exploited. To address this, we have designed a scalable microfluidic hydrodynamic focusing (MHF)technology for the controllable, rapid, and continuous production of lyotropic liquid crystalline (LLC) nanoparticles (both cubosomes andhexosomes), colloidal dispersions of higher-order lipid assemblies with intricate internal structures of 3-D and 2-D symmetry. These particleshave been proposed as the next generation of soft-matter nano-carriers, with unique fusogenic and physical properties. Crucially, unlikealternative approaches, our microfluidic method gives control over LLC size, a feature we go on to exploit in a fusogenic study with modelcell membranes, where a dependency on particle diameter is evident. We believe our platform has the potential to serve as a tool for futurestudies involving non-lamellar soft nanoparticles, and anticipate it allowing for the rapid prototyping of LLC particles of diverse functionality,paving the way toward their eventual uptake at an industrial level.
Saurabh S, Kalonia C, Li Z, et al., 2023, All atom molecular dynamics simulations of the interfacial behaviour of mAbs, Publisher: SPRINGER, Pages: S205-S205, ISSN: 0175-7571
Saurabh S, Kalonia C, Li Z, et al., 2022, Understanding the stabilizing effect of histidine on mAb aggregation: a molecular dynamics study., Molecular Pharmaceutics, Vol: 19, ISSN: 1543-8384
Histidine, a widely used buffer in monoclonal antibody (mAb) formulations, is known to reduce antibody aggregation. While experimental studies suggest a nonelectrostatic, nonstructural (relating to secondary structure preservation) origin of the phenomenon, the underlying microscopic mechanism behind the histidine action is still unknown. Understanding this mechanism will help evaluate and predict the stabilizing effect of this buffer under different experimental conditions and for different mAbs. We have used all-atom molecular dynamics simulations and contact-based free energy calculations to investigate molecular-level interactions between the histidine buffer and mAbs, which lead to the observed stability of therapeutic formulations in the presence of histidine. We reformulate the Spatial Aggregation Propensity index by including the buffer-protein interactions. The buffer adsorption on the protein surface leads to lower exposure of the hydrophobic regions to water. Our analysis indicates that the mechanism behind the stabilizing action of histidine is connected to the shielding of the solvent-exposed hydrophobic regions on the protein surface by the buffer molecules.
Abdel Aty H, Strutt R, Mcintyre N, et al., 2022, Machine learning platform for determining experimental lipid phase behaviour from small angle X-ray scattering patterns by pre-training on synthetic data, Digital Discovery, Vol: 1, Pages: 98-107
Lipid membranes are vital in a wide range of biological and biotechnical systems; they undepin functions from modulation of protein activity to drug uptake and delivery. Understanding the structure, interactions, self-assembly and phase behaviour of lipids is critical to developing a molecular undertanding of biological membrane mediated processes, establishing engineering approaches to biotechnical membrane application development. Small Angle X-ray Scattering (SAXS) is the de facto method used to analyse the structure of self-assembled lipid systems. The resultant diffraction patterns are however extremely difficult to assign automatically with researchers spending considerable time often analysing patterns ex situ from a beamline facility, reducing experimental capacity and optimisation. Furthermore, research projects will often focus on particular lipid compositions and thus would benefit significantly from a method which can be rapidly optimised for a range of samples of interest. We present a generalisable machine learning pipeline that is able to classify lipid phases based on their raw, experimental SAXS spectra, with >99% accuracy and an inference time of <60 ms, enabling high throughput on-site analysis. We achieved this through application of a synthetic data generation system, capable of building synthetic SAXS patterns from the underlying physics which dictate phase behaviour, and we also propose an extension of our system to synthetically generate co-existence phase spectra with known composition ratios. Pre-training our machine learning model on this synthetic data, and fine-tuning on experimental samples empowers the model in achieving state-of-the-art, rapid lipid phase classification, allowing researchers to be able to adapt their experiments on site if needed and hence massively accelerate high throughput lipid research.
Aguilar M-I, Al Nahas K, Barrera FN, et al., 2021, Theoretical and experimental comparisons of simple peptide-membrane systems; towards defining the reaction space: general discussion, FARADAY DISCUSSIONS, Vol: 232, Pages: 149-171, ISSN: 1359-6640
Xu Z, Seddon JM, Beales PA, et al., 2021, Breaking Isolation to Form New Networks: pH-Triggered Changes in Connectivity inside Lipid Nanoparticles, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 143, Pages: 16556-16565, ISSN: 0002-7863
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- Citations: 10
Allen ME, Elani Y, Brooks NJ, et al., 2021, The effect of headgroup methylation on polymorphic phase behaviour in hydrated N-methylated phosphoethanolamine: palmitic acid membranes, Soft Matter, Vol: 17, Pages: 5763-5771, ISSN: 1744-683X
Mixtures of fatty acids and phospholipids can form hexagonal (HII) and inverse bicontinuous cubic phases, the latter of which are implicated in various cellular processes and have wide-ranging biotechnological applications in protein crystallisation and drug delivery systems. Therefore, it is vitally important to understand the formation conditions of inverse bicontinuous cubic phases and how their properties can be tuned. We have used differential scanning calorimetry and synchrotron-based small angle and wide angle X-ray scattering (SAXS/WAXS) to investigate the polymorphic phase behaviour of palmitic acid/ partially-methylated phospholipid mixtures, and how headgroup methylation impacts on inverse bicontinuous cubic phase formation. We find that upon partial methylation of the phospholipid headgroup (1 or 2 methyl substituents) inverse bicontinuous cubic phases are formed (of the Im3m spacegroup), which is not the case with 0 or 3 methyl substituents. This shows how important headgroup methylation is for controlling phase behaviour and how a change in headgroup methylation can be used to controllably tune various inverse bicontinuous phase features such as their lattice parameter and the temperature range of their stability.
Pilkington CP, Seddon JM, Elani Y, 2021, Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies., Physical Chemistry Chemical Physics, Vol: 23, Pages: 3693-3706, ISSN: 1463-9076
Microfluidics has been proposed as an attractive alternative to conventional bulk methods used in the generation of self-assembled biomimetic structures, particularly where there is a desire for more scalable production. The approach also allows for greater control over the self-assembly process, and parameters such as particle architecture, size, and composition can be finely tuned. Microfluidic techniques used in the generation of microscale assemblies (giant vesicles and higher-order multi-compartment assemblies) are fairly well established. These tend to rely on microdroplet templation, and the resulting structures have found use as comparmentalised motifs in artificial cells. Challenges in generating sub-micron droplets have meant that reconfiguring this approach to form nano-scale structures is not straightforward. This is beginning to change however, and recent technological advances have instigated the manufacture and manipulation of an increasingly diverse repertoire of biomimetic nano-assemblies, including liposomes, polymersomes, hybrid particles, multi-lamellar structures, cubosomes, hexosomes, nanodiscs, and virus-like particles. The following review will discuss these higher-order self-assembled nanostructures, including their biochemical and industrial applications, and techniques used in their production and analysis. We suggest ways in which existing technologies could be repurposed for the enhanced design, manufacture, and exploitation of these structures and discuss potential challenges and future research directions. By compiling recent advances in this area, it is hoped we will inspire future efforts toward establishing scalable microfluidic platforms for the generation of biomimetic nanoparticles of enhanced architectural and functional complexity.
Carter JW, Gonzalez MA, Brooks NJ, et al., 2020, Flip-flop asymmetry of cholesterol in model membranes induced by thermal gradients, Soft Matter, Vol: 16, Pages: 5925-5932, ISSN: 1744-683X
Lipid asymmetry is a crucial property of biological membranes and significantly influences their physical and mechanical properties. It is responsible for maintaining different chemical environments on the external and internal surfaces of cells and organelles and plays a vital role in many biological processes such as cell signalling and budding. In this work we show, using non-equilibrium molecular dynamics (NEMD) simulations, that thermal fields can induce lipid asymmetry in biological membranes. We focus our investigation on cholesterol, an abundant lipid in the plasma membrane, with a rapid flip-flop rate, significantly influencing membrane properties. We demonstrate that thermal fields induce membrane asymmetry with cholesterol showing thermophobic behaviour and therefore accumulating on the cold side of the membrane. This work highlights a possible experimental route to preparing and controlling asymmetry in synthetic membranes.
Weatherby S, Seddon JM, Ceroni P, 2020, Luminescent silicon nanostructures and COVID-19, FARADAY DISCUSSIONS, Vol: 222, Pages: 8-9, ISSN: 1359-6640
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- Citations: 3
Tascini AS, Wang S, Seddon JM, et al., 2020, Fats’ love–hate relationships: a molecular dynamics simulation and hands-on experiment outreach activity to introduce the amphiphilic nature and biological functions of lipids to young students and the general public, Journal of Chemical Education, Vol: 97, Pages: 1360-1367, ISSN: 0021-9584
Lipids are fundamental components of biological organisms and have important applications in the pharmaceutical, food, and cosmetics industries. Thus, it is important that young students and the general public properly understand the basic properties of lipids and how these relate to their biological and industrial roles. Here, we use molecular dynamics computer simulations and a simple, safe, and inexpensive popular hands-on activity, to communicate to participants why and how lipid molecules play a fundamental role in all living organisms and in our bodies. The activity is called “Fats’ Love–Hate Relationships”, to highlight how the different parts of amphiphilic lipids interact with water. This “love–hate relationship” is vital to the biological functions of lipids and drives the formation of lipid structures that can be visualized at molecular scale with the computer simulations. The participants were encouraged to investigate the interactions between milk lipids and soap surfactants, creating beautiful complex artwork that they could then take home. The hands-on activity was accompanied by a video of a molecular simulation that illustrates milk–soap interactions at a molecular scale and helps to explain how the amphiphilicity of lipids creates the beautiful artwork at a molecular level. The outreach activity has been performed in science festivals and in classrooms and has been well received by participants of all ages with multiple learner comprehension levels (primary and secondary school students and the general public). By combining molecular simulation, explanations of the amphiphilic structure of the lipids, and an engaging hands-on activity, we explained how lipids interact with water and surfactants and inspired discussions on the link between the structure of the lipids and their biological function, namely, their structural and protective roles as a key component of cell membranes.
Barriga H, Ces O, Law R, et al., 2019, Engineering swollen cubosomes using cholesterol and anionic lipids, Langmuir: the ACS journal of surfaces and colloids, Vol: 35, Pages: 16521-16527, 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
Biological membranes constantly modulate their fluidity for proper functioning of the cell. Modulation of membrane properties via regulation of fatty acid composition has gained a renewed interest owing to its relevance in endocytosis, endoplasmic reticulum membrane homeostasis, and adaptation mechanisms in the deep sea. Endowed with significant degrees of freedom, the presence of free fatty acids can alter the curvature of membranes which in turn can alter the response of curvature sensing proteins, thus defining adaptive ways to reconfigure membranes. Most significantly, recent experiments demonstrated that polyunsaturated lipids facilitate membrane bending and fission by endocytic proteins – the first step in the biogenesis of synaptic vesicles. Despite the vital roles of fatty acids, a systematic study relating the interactions between fatty acids and membrane and the consequent effect on the bio-mechanics of membranes under the influence of fatty acids has been sparse. Of specific interest is the vast disparity in the properties of cis and trans fatty acids, that only differ in the orientation of the double bond and yet have entirely unique and opposing chemical properties. Here we demonstrate a combined X-ray diffraction and membrane fluctuation analysis method to couple the structural properties to the biophysical properties of fatty acid-laden membranes to address current gaps in our understanding. By systematically doping pure dioleoyl phosphatidylcholine (DOPC) membranes with cis fatty acid and trans fatty acid we demonstrate that the presence of fatty acids doesn’t always fluidize the membrane. Rather, an intricate balance between the curvature, molecular interactions, as well as the amount of specific fatty acid dictates the fluidity of membranes. Lower concentrations are dominated by the nature of interactions between the phospholipid and the fatty acids. Trans fatty acid increases the rigidity while decreasing the area per lipid similar to
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 α-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
The effect of glycerol with sodium chloride (NaCl) on the phase behaviour of sodium dodecyl sulfate (SDS) near the Krafft point was studied by surface tension analysis using the pendant drop method. The critical micelle concentration (CMC) and Krafft Temperature (TK) of SDS in water: glycerol mixtures, across the full composition range, and in NaCl solutions within 0.005–0.1 M were obtained. The pendant drop method successfully allowed us to determine the Krafft point of SDS in high glycerol systems where other traditional methods (e.g. conductivity) have been ineffective. Overall the addition of glycerol increases the CMC and the TK, thus shifting the Krafft point of SDS to higher temperatures (increasing crystallisation temperatures) and higher SDS content in the presence of glycerol, which is interpreted as a result of the reduction in solvent polarity which opposes micellization. The addition of NaCl to the SDS – water-glycerol systems brings the CMC back down, while having no significant effect on the TK. Our results establish a robust route for tuning the Krafft point of model surfactant SDS by adjusting solvent quality and salt content.
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
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