Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleMcCarthy N, Chan C, Mignini Urdaneta G, et al., 2024,
The effect of hydrostatic pressure on lipid membrane lateral structure
, Methods in Enzymology, Vol: 700, Pages: 49-76, ISSN: 0076-6879High pressure is both an environmental challenge to which deep sea biology has to adapt, and a highly sensitive thermodynamic tool that can be used to trigger structural changes in biological molecules and assemblies. Lipid membranes are amongst the most pressure sensitive biological assemblies and pressure can have a large influence on their structure and properties. In this chapter, we will explore the use of high pressure small angle X-ray diffraction and high pressure microscopy to measure and quantify changes in the lateral structure of lipid membranes under both equilibrium high pressure conditions and in response to pressure jumps.
-
Journal articleGovey-Scotland J, Johnstone L, Myant C, et al., 2023,
Towards a skin-on-a-chip for screening the dermal absorption of cosmetics
, Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 23, Pages: 5068-5080, ISSN: 1473-0189Over the past few decades, there have been increasing global efforts to limit or ban the use of animals for testing cosmetic products. This ambition has been at the heart of international endeavours to develop new in vitro and animal-free approaches for assessing the safety of cosmetics. While several of these new approach methodologies (NAMs) have been approved for assessing different toxicological endpoints in the UK and across the EU, there remains an absence of animal-free methods for screening for dermal absorption; a measure that assesses the degree to which chemical substances can become systemically available through contact with human skin. Here, we identify some of the major technical barriers that have impacted regulatory recognition of an in vitro skin model for this purpose and propose how these could be overcome on-chip using artificial cells engineered from the bottom-up. As part of our future perspective, we suggest how this could be realised using a digital biomanufacturing pipeline that connects the design, microfluidic generation and 3D printing of artificial cells into user-crafted synthetic tissues. We highlight milestone achievements towards this goal, identify future challenges, and suggest how the ability to engineer animal-free skin models could have significant long-term consequences for dermal absorption screening, as well as for other applications.
-
Journal articleAdamala KP, Dogterom M, Elani Y, et al., 2023,
Present and future of synthetic cell development
, NATURE REVIEWS MOLECULAR CELL BIOLOGY, ISSN: 1471-0072 -
Journal articleRaguseo F, Wang Y, Li J, et al., 2023,
The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes
, Nature Communications, Vol: 14, ISSN: 2041-1723Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is expansion of the intronic hexanucleotide repeat (GGGGCC)n in C9orf72. Here, we investigate the formation of nucleic acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of ALS/FTD. We observe significant aggregation of the hexanucleotide sequence (GGGGCC)n, which we associate to the formation of multimolecular G-quadruplexes (mG4s) by using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions leads to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validate the biological relevance of our findings by detecting an increased prevalence of G4-structures in C9orf72 mutant human motor neurons when compared to healthy motor neurons by staining with a G4-selective fluorescent probe, revealing signal in putative condensates. Our findings strongly suggest that RNA G-rich repetitive sequences can form protein-free condensates sustained by multimolecular G-quadruplexes, highlighting their potential relevance as therapeutic targets for C9orf72 mutation-related ALS/FTD.
-
Journal articleYang M, Cui J, Daboczi M, et al., 2023,
Interplay between Collective and Localized Effects of Point Defects on Photoelectrochemical Performance of TiO<sub>2</sub> Photoanodes for Oxygen Evolution
, ADVANCED MATERIALS INTERFACES, Vol: 10, ISSN: 2196-7350 -
Journal articleWalter V, Bi D, Salehi-Reyhani A, et al., 2023,
Real-time signal processing via chemical reactions for a microfluidic molecular communication system
, NATURE COMMUNICATIONS, Vol: 14 -
Journal articleCruz-Samperio R, Hicks CL, Scott A, et al., 2023,
Modular Bioorthogonal Lipid Nanoparticle Modification Platforms for Cardiac Homing
, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 145, Pages: 22659-22670, ISSN: 0002-7863 -
Journal articleElani Y, Seddon J, 2023,
What it means to be alive: a synthetic cell perspective
, Interface Focus, Vol: 13, Pages: 1-3, ISSN: 2042-8898Advances 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.
-
Journal articleSaurabh 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: 0026-8976The 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.
-
Journal articleAllen ME, Hindley J, O'Toole N, et al., 2023,
Biomimetic Behaviours in Hydrogel Artificial Cells through Embedded Organelles
, Proceedings of the National Academy of Sciences of USA, Vol: 120, ISSN: 0027-8424Artificial cells are biomimetic structures formed from molecular building blocks that replicate biological processes, behaviors, and architectures. Of these building blocks, hydrogels have emerged as ideal, yet underutilized candidates to provide a gel-like chassis in which to incorporate both biological and nonbiological componentry which enables the replication of cellular functionality. Here, we demonstrate a microfluidic strategy to assemble biocompatible cell-sized hydrogel-based artificial cells with a variety of different embedded functional subcompartments, which act as engineered synthetic organelles. The organelles enable the recreation of increasingly biomimetic behaviors, including stimulus-induced motility, content release through activation of membrane-associated proteins, and enzymatic communication with surrounding bioinspired compartments. In this way, we showcase a foundational strategy for the bottom–up construction of hydrogel-based artificial cell microsystems which replicate fundamental cellular behaviors, paving the way for the construction of next-generation biotechnological devices.
-
Journal articlePaez-Perez M, Dent MRR, Brooks NJJ, et al., 2023,
Viscosity-sensitive membrane dyes as tools to estimate the crystalline structure of lipid bilayers
, Analytical Chemistry, Vol: 95, Pages: 12006-12014, ISSN: 0003-2700Lipid membranes are crucial for cellular integrity and regulation, and tight control of their structural and mechanical properties is vital to ensure that they function properly. Fluorescent probes sensitive to the membrane’s microenvironment are useful for investigating lipid membrane properties; however, there is currently a lack of quantitative correlation between the exact parameters of lipid organization and a readout from these dyes. Here, we investigate this relationship for “molecular rotors”, or microviscosity sensors, by simultaneously measuring their fluorescence lifetime to determine the membrane viscosity, while using X-ray diffraction to determine the membrane’s structural properties. Our results reveal a phase-dependent correlation between the membrane’s structural parameters and mechanical properties measured by a BODIPY-based molecular rotor, giving excellent predictive power for the structural descriptors of the lipid bilayer. We also demonstrate that differences in membrane thickness between different lipid phases are not a prerequisite for the formation of lipid microdomains and that this requirement can be disrupted by the presence of line-active molecules. Our results underpin the use of membrane-sensitive dyes as reporters of the structure of lipid membranes.
-
Journal articlePilkington 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: 2045-2322Soft-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.
-
Conference paperSaurabh 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 -
Journal articleHo SKY, Ezeorah C, Chari S, et al., 2023,
Monitoring light‐driven oxygen insertion reactions into metal carbon bonds by LED‐NMR spectroscopy
, ChemPhotoChem, Vol: 7, Pages: 1-6, ISSN: 2367-0932The facile light-driven insertion reaction of oxygen into metal carbon bonds of the BPI (1,3-bis(2-pyridylimino)isoindole) complexes [Pt(BPI)Me] and [Pd(BPI)Me] has been investigated by LED-NMR in CDCl3. The initial insertion reaction leads to peroxo complexes [Pt(BPI)OOMe] and [Pd(BPI)OOMe], which undergo further reactions over time. Spectra were recorded at 1 minute time intervals, which enabled the tracking of the methyl substituent, which eventually generates formaldehyde (and methanediol) and methanol in almost equal proportions. Degradation of the solvent CDCl3 to phosgene and DCl in the presence of oxygen and light leads to several side reactions. DCl reacts with [M(BPI)Me] and [M(BPI)OOMe] to form [M(BPI)Cl], whereas phosgene reacts with in situ generated methanol to chloro methylformate and dimethyl carbonate.
-
Journal articleSupramaniam P, Wang Z, Chatzimichail S, et al., 2023,
Measuring encapsulation efficiency in cell-mimicking giant unilamellar vesicles
, ACS Synthetic Biology, Vol: 12, Pages: 1227-1238, ISSN: 2161-5063One of the main drivers within the field of bottom-up synthetic biology is to develop artificial chemical machines, perhaps even living systems, that have programmable functionality. Numerous toolkits exist to generate giant unilamellar vesicle-based artificial cells. However, methods able to quantitatively measure their molecular constituents upon formation is an underdeveloped area. We report an artificial cell quality control (AC/QC) protocol using a microfluidic-based single-molecule approach, enabling the absolute quantification of encapsulated biomolecules. While the measured average encapsulation efficiency was 11.4 ± 6.8%, the AC/QC method allowed us to determine encapsulation efficiencies per vesicle, which varied significantly from 2.4 to 41%. We show that it is possible to achieve a desired concentration of biomolecule within each vesicle by commensurate compensation of its concentration in the seed emulsion. However, the variability in encapsulation efficiency suggests caution is necessary when using such vesicles as simplified biological models or standards.
-
Journal articleKoutsoukos S, Avila J, Brooks NJJ, et al., 2023,
Physical properties and nanostructuring of long-chained homobaric imidazolium ionic liquids
, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 25, Pages: 6316-6325, ISSN: 1463-9076 -
Journal articlePaez Perez M, Dent MR, Brooks N, et al., 2023,
Directly imaging emergence of phase separation in peroxidized lipid membranes
, Communications Chemistry, ISSN: 2399-3669 -
Journal articleGispert Contamina I, Hindley J, Pilkington C, et al., 2022,
Stimuli-responsive vesicles as distributed artificial organelles for bacterial activation
, Proceedings of the National Academy of Sciences of USA, Vol: 119, Pages: 1-10, ISSN: 0027-8424Intercellular communication is a hallmark of living systems. As such, engineering artificial cells that possess this behavior has been at the heart of activities in bottom-up synthetic biology. Communication between artificial and living cells has potential to confer novel capabilities to living organisms that could be exploited in biomedicine and biotechnology. However, most current approaches rely on the exchange of chemical signals that cannot be externally controlled. Here, we report two types of remote-controlled vesicle-based artificial organelles that translate physical inputs into chemical messages that lead to bacterial activation. Upon light or temperature stimulation, artificial cell membranes are activated, releasing signaling molecules that induce protein expression in Escherichia coli. This distributed approach differs from established methods for engineering stimuli-responsive bacteria. Here, artificial cells (as opposed to bacterial cells themselves) are the design unit. Having stimuli-responsive elements compartmentalized in artificial cells has potential applications in therapeutics, tissue engineering, and bioremediation. It will underpin the design of hybrid living/nonliving systems where temporal control over population interactions can be exerted.
-
Journal articleSaurabh 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: 1543-8384Histidine, 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.
-
Journal articleAllen ME, Hindley JW, Baxani DK, et al., 2022,
Hydrogels as functional components in artificial cell systems
, Nature Reviews Chemistry, Vol: 6, Pages: 562-578, ISSN: 2397-3358Recent years have seen substantial efforts aimed at constructing artificial cells from various molecular components with the aim of mimicking the processes, behaviours and architectures found in biological systems. Artificial cell development ultimately aims to produce model constructs that progress our understanding of biology, as well as forming the basis for functional bio-inspired devices that can be used in fields such as therapeutic delivery, biosensing, cell therapy and bioremediation. Typically, artificial cells rely on a bilayer membrane chassis and have fluid aqueous interiors to mimic biological cells. However, a desire to more accurately replicate the gel-like properties of intracellular and extracellular biological environments has driven increasing efforts to build cell mimics based on hydrogels. This has enabled researchers to exploit some of the unique functional properties of hydrogels that have seen them deployed in fields such as tissue engineering, biomaterials and drug delivery. In this Review, we explore how hydrogels can be leveraged in the context of artificial cell development. We also discuss how hydrogels can potentially be incorporated within the next generation of artificial cells to engineer improved biological mimics and functional microsystems.
-
Journal articleZubaite G, Hindley JW, Ces O, et al., 2022,
Dynamic reconfiguration of subcompartment architectures in artificial cells.
, ACS Nano, Vol: 16, ISSN: 1936-0851Artificial cells are minimal structures constructed from biomolecular building blocks designed to mimic cellular processes, behaviors, and architectures. One near-ubiquitous feature of cellular life is the spatial organization of internal content. We know from biology that organization of content (including in membrane-bound organelles) is linked to cellular functions and that this feature is dynamic: the presence, location, and degree of compartmentalization changes over time. Vesicle-based artificial cells, however, are not currently able to mimic this fundamental cellular property. Here, we describe an artificial cell design strategy that addresses this technological bottleneck. We create a series of artificial cell architectures which possess multicompartment assemblies localized either on the inner or on the outer surface of the artificial cell membrane. Exploiting liquid-liquid phase separation, we can also engineer spatially segregated regions of condensed subcompartments attached to the cell surface, aligning with coexisting membrane domains. These structures can sense changes in environmental conditions and respond by reversibly transitioning from condensed multicompartment layers on the membrane surface to a dispersed state in the cell lumen, mimicking the dynamic compartmentalization found in biological cells. Likewise, we engineer exosome-like subcompartments that can be released to the environment. We can achieve this by using two types of triggers: chemical (addition of salts) and mechanical (by pulling membrane tethers using optical traps). These approaches allow us to control the compartmentalization state of artificial cells on population and single-cell levels.
-
Journal articleContini C, Hu W, Elani Y, 2022,
Manufacturing polymeric porous capsules
, Chemical Communications, Vol: 58, Pages: 4409-4419, ISSN: 1359-7345Polymeric porous capsules represent hugely promising systems that allow a size-selective through-shell material exchange with their surroundings. They have vast potential in applications ranging from drug delivery and chemical microreactors to artificial cell science and synthetic biology. Due to their porous core-shell structure, polymeric porous capsules possess an enhanced permeability that enables the exchange of small molecules while retaining larger compounds and macromolecules. The cross-capsule transfer of material is regulated by their pore size cut-off, which depends on the molecular composition and adopted fabrication method. This review outlines the main strategies adopted for manufacturing polymeric porous capsules to provide some practical guidance for designing polymeric capsules with controlled pore size.
-
Journal articleStrutt R, Sheffield F, Barlow N, et al., 2022,
UV-DIB: label-free permeability determination using droplet interface bilayers
, Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 22, Pages: 972-985, ISSN: 1473-0189Simple diffusion of molecular entities through a phospholipid bilayer, is a phenomenon of great importance to the pharmaceutical and agricultural industries. Current model lipid systems to probe this typically only employ fluorescence as a readout, thus limiting the range of assessable chemical matter that can be studied. We report a new technology platform, the UV-DIB, which facilitates label free measurement of small molecule translocation rates. This is based upon the coupling of droplet interface bilayer technology with implemented fiber optics to facilitate analysis via ultraviolet spectroscopy, in custom designed PMMA wells. To improve on current DIB technology, the platform was designed to be reusable, with a high sampling rate and a limit of UV detection in the low μM regime. We demonstrate the use of our system to quantify passive diffusion in a reproducible and rapid manner where the system was validated by investigating multiple permeants of varying physicochemical properties across a range of lipid interfaces, each demonstrating differing kinetics. Our system permits the interrogation of structural dependence on the permeation rate of a given compound. We present this ability from two structural perspectives, that of the membrane, and the permeant. We observed a reduction in permeability between pure DOPC and DPhPC interfaces, concurring with literature and demonstrating our ability to study the effects of lipid composition on permeability. In relation to the effects of permeant structure, our device facilitated the rank ordering of various compounds from the xanthine class of compounds, where the structure of each permeant differed by a single group alteration. We found that DIBs were stable up to 5% DMSO, a molecule often used to aid solubilisation of pharmaceutical and agrochemical compounds. The ability of our device to rank-order compounds with such minor structural differences provides a level of precision that is rarely seen in current, industr
-
Journal articleAbdel 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: 98-107Lipid 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.
-
Journal articleMonck C, Elani Y, Ceroni F, 2022,
Cell-free protein synthesis: biomedical applications and future perspectives
, Chemical Engineering Research and Design, Vol: 177, Pages: 653-658, ISSN: 0263-8762The use of cell-free protein synthesis (CFPS) has become increasingly widespread in synthetic biology over recent years, providing an effective platform for the study and engineering of cellular processes. The versatility and portability of CFPS systems have also boosted their potential for usage outside of the laboratory in a wide number of applications, from construct prototyping to bioproduction. CFPS is particularly well suited to biomedical applications, such as the production of clinical molecules and vaccines. It can also be integrated with additional technologies such as microfluidics and liposomal encapsulation to provide a new route for on-demand therapeutic expression. In this review we outline the key features of CFPS that make it a powerful platform for biomedical applications. We also discuss existing limitations with respect to the use of CFPS in the production of complex protein products and the limited production capacity of current systems. Addressing these will be integral in expanding the application of CFPS in biotherapy
-
Journal articleAguilar 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 -
Journal articleAllen ME, Albon J, Elani Y, 2021,
Layer-by-layer assembly of multi-layered droplet interface bilayers (multi-DIBs)
, Chemical Communications, Vol: 58, Pages: 60-63, ISSN: 1359-7345Droplet interface bilayers (DIBs) have tremendous promise as platforms for fundamental biomembrane studies and in biotechnology. Being composed of a single bilayer however limits their biomimetic potential, as many cell membrane motifs are composed of multiple aligned bilayers. We describe a technology to manufacture cell-sized multi-layered DIBs (multi-DIBs) by coating giant unilamellar vesicles with a further monolayer, and allowing such structures to make contact with themselves or a monolayer coated droplet. This easily customisable strategy will pave the way for an expanded repertoire of DIB functionality, for example by facilitating the incorporation of multiple-bilayer spanning protein complexes.
-
Journal articleMolisso S, Williams DR, Ces O, et al., 2021,
Molecular interaction and partitioning in α-Keratin using 1H NMR Spin-Lattice (T1) relaxation times
, Journal of the Royal Society Interface, Vol: 18, Pages: 1-8, ISSN: 1742-5662The interactions between small molecules and keratins are poorly understood. In this paper an NMR method is presented to measure changes in the 1H T1 relaxation times of small molecules in human hair keratin to quantify their interaction with the fiber. Two populations of small molecule compounds were identified with distinct relaxation times, demonstrating the partitioning of the compounds into different keratin environments. The changes in relaxation time for solvent in hair compared to bulk solvent were shown to be related to the molecular weight, MW, and the partition coefficient, LogP, of the solvent investigated. Compounds with low molecular weights and high hydrophilicities had greater reductions in their T1 relaxation times and therefore experienced increased interactions with the hair fiber. The relative population sizes were also calculated. This is a significant step toward modelling the behavior of small molecules in keratinous materials and other large insoluble fibrous proteins.
-
Journal articleSalvador-Castell M, Golub M, Erwin N, et al., 2021,
Characterisation of a synthetic Archeal membrane reveals a possible new adaptation route to extreme conditions
, Communications Biology, Vol: 4, Pages: 1-13, ISSN: 2399-3642It has been proposed that adaptation to high temperature involved the synthesis of monolayer-forming ether phospholipids. Recently, a novel membrane architecture was proposed to explain the membrane stability in polyextremophiles unable to synthesize such lipids, in which apolar polyisoprenoids populate the bilayer midplane and modify its physico-chemistry, extending its stability domain. Here, we have studied the effect of the apolar polyisoprenoid squalane on a model membrane analogue using neutron diffraction, SAXS and fluorescence spectroscopy. We show that squalane resides inside the bilayer midplane, extends its stability domain, reduces its permeability to protons but increases that of water, and induces a negative curvature in the membrane, allowing the transition to novel non-lamellar phases. This membrane architecture can be transposed to early membranes and could help explain their emergence and temperature tolerance if life originated near hydrothermal vents. Transposed to the archaeal bilayer, this membrane architecture could explain the tolerance to high temperature in hyperthermophiles which grow at temperatures over 100 °C while having a membrane bilayer. The induction of a negative curvature to the membrane could also facilitate crucial cell functions that require high bending membranes.
-
Journal articlePazos MD, Hu Y, Elani Y, et al., 2021,
Tattoo inks for optical biosensing in interstitial fluid
, Advanced Healthcare Materials, Vol: 10, Pages: 1-22, ISSN: 2192-2640The persistence of traditional tattoo inks presents an advantage for continuous andlong-term health monitoring in point of care devices. The replacement of tattoo pigments withoptical biosensors aims a promising alternative for monitoring blood biomarkers. Tattoo inksfunctionalization enables the control of interstitial biomarkers with correlated concentrations inplasma, to diagnose diseases, evaluate progression, and prevent complications associated withphysio pathological disorders or medication mismatches. The specific biomarkers in interstitialfluid provide a new source of information, especially for skin diseases. The study of tattoo inksdisplays insufficient regulation in their composition, a lack of reports of the relatedcomplications and a need for further studies on their degradation kinetics. This review focuseson tattoo optical biosensors for monitoring dermal interstitial biomarkers and discusses theyclinical advantages and main challenges for in vivo implantation. Tattoo functionalizationprovides a minimally invasive, reversible, biocompatible, real-time sensing with long-termpermanence and multiplexing capabilities for the control, diagnosis, and prevention of illness;it enables self-controlling management by the patient, but also the possibility of sending therecords to the doctor.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.
Contact Us
For more information, please contact one of the Group Leaders: