Imperial College London

Dr Nick Brooks

Faculty of Natural SciencesDepartment of Chemistry

Reader in Membrane Biophysics
 
 
 
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Contact

 

+44 (0)20 7594 2677n.brooks Website

 
 
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Location

 

207JMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

106 results found

Neville GM, Dobre A-M, Smith GJ, Micciulla S, Brooks NJ, Arnold T, Welton T, Edler KJet al., 2023, Interactions of Choline and Geranate (CAGE) and Choline Octanoate (CAOT) Deep Eutectic Solvents with Lipid Bilayers, ADVANCED FUNCTIONAL MATERIALS, ISSN: 1616-301X

Journal article

Paez-Perez M, Dent MRR, Brooks NJJ, Kuimova MKKet al., 2023, Viscosity-Sensitive Membrane Dyes as Tools To Estimate the Crystalline Structure of Lipid Bilayers, ANALYTICAL CHEMISTRY, Vol: 95, Pages: 12006-12014, ISSN: 0003-2700

Journal article

Koutsoukos S, Avila J, Brooks NJJ, Gomes MC, Welton Tet 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 article

Paez Perez M, Dent MR, Brooks N, Kuimova Met al., 2023, Directly imaging emergence of phase separation in peroxidized lipid membranes, Communications Chemistry, ISSN: 2399-3669

Journal article

Strutt R, Sheffield F, Barlow N, Flemming AJ, Harling JD, Law RV, Brooks NJ, Barter LMC, Ces Oet 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: 1473-0189

Simple 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 article

Abdel Aty H, Strutt R, Mcintyre N, Allen M, Barlow NE, Páez-Pérez M, Seddon JM, Brooks N, Ces O, Gould IRet 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.

Journal article

Salvador-Castell M, Golub M, Erwin N, Demé B, Brooks NJ, Winter R, Peters J, Oger PMet 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: 2399-3642

It 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 article

Mora NL, Findlay HE, Brooks NJ, Purushothaman S, Ces O, Booth PJet al., 2021, The membrane transporter lactose permease increases lipid bilayer bending rigidity, BIOPHYSICAL JOURNAL, Vol: 120, Pages: 3787-3794, ISSN: 0006-3495

Journal article

Ip T, Li Q, Brooks N, Elani Yet al., 2021, Manufacture of multilayered artificial cell membranes through sequential bilayer deposition on emulsion templates., ChemBioChem: a European journal of chemical biology, Vol: 22, Pages: 2275-2281, ISSN: 1439-4227

Efforts to manufacture artificial cells that replicate the architectures, processes and behaviours of biological cells are rapidly increasing. Perhaps the most commonly reconstructed cellular structure is the membrane, through the use of unilamellar vesicles as models. However, many cellular membranes, including bacterial double membranes, nuclear envelopes, and organelle membranes, are multilamellar. Due to a lack of technologies available for their controlled construction, multilayered membranes are not part of the repertoire of cell-mimetic motifs used in bottom-up synthetic biology. To address this, we developed emulsion-based technologies that allow cell-sized multilayered vesicles to be produced layer-by-layer, with compositional control over each layer, thus enabling studies that would otherwise remain inaccessible. We discovered that bending rigidities scale with the number of layers and demonstrate inter-bilayer registration between coexisting liquid-liquid domains. These technologies will contribute to the exploitation of multilayered membrane structures, paving the way for incorporating protein complexes that span multiple bilayers.

Journal article

Allen ME, Elani Y, Brooks NJ, Seddon Jet 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.

Journal article

Salvador-Castell M, Brooks NJ, Winter R, Peters J, Oger PMet al., 2021, Non-polar lipids as regulators of membrane properties in archaeal lipid bilayer mimics, International Journal of Molecular Sciences, Vol: 22, Pages: 6087-6087, ISSN: 1422-0067

The modification of archaeal lipid bilayer properties by the insertion of apolar molecules in the lipid bilayer midplane has been proposed to support cell membrane adaptation to extreme environmental conditions of temperature and hydrostatic pressure. In this work, we characterize the insertion effects of the apolar polyisoprenoid squalane on the permeability and fluidity of archaeal model membrane bilayers, composed of lipid analogues. We have monitored large molecule and proton permeability and Laurdan generalized polarization from lipid vesicles as a function of temperature and hydrostatic pressure. Even at low concentration, squalane (1 mol%) is able to enhance solute permeation by increasing membrane fluidity, but at the same time, to decrease proton permeability of the lipid bilayer. The squalane physicochemical impact on membrane properties are congruent with a possible role of apolar intercalants on the adaptation of Archaea to extreme conditions. In addition, such intercalant might be used to cheaply create or modify chemically resistant liposomes (archeaosomes) for drug delivery.

Journal article

Paez-Perez M, Lopez-Duarte I, Vysniauskas A, Brooks NJ, Kuimova MKet al., 2021, Imaging non-classical mechanical responses of lipid membranes using molecular rotors, Chemical Science, Vol: 12, Pages: 2604-2613, ISSN: 2041-6520

Lipid packing in cellular membranes has a direct effect on membrane tension and microviscosity, and plays a central role in cellular adaptation, homeostasis and disease. According to conventional mechanical descriptions, viscosity and tension are directly interconnected, with increased tension leading to decreased membrane microviscosity. However, the intricate molecular interactions that combine to build the structure and function of a cell membrane suggest a more complex relationship between these parameters. In this work, a viscosity-sensitive fluorophore (‘molecular rotor’) is used to map changes in microviscosity in model membranes under conditions of osmotic stress. Our results suggest that the relationship between membrane tension and microviscosity is strongly influenced by the bilayer's lipid composition. In particular, we show that the effects of increasing tension are minimised for membranes that exhibit liquid disordered (Ld) – liquid ordered (Lo) phase coexistence; while, surprisingly, membranes in pure gel and Lo phases exhibit a negative compressibility behaviour, i.e. they soften upon compression.

Journal article

Shimolina LE, Gulin AA, Paez-Perez M, Lopez-Duarte I, Druzhkova IN, Lukina MM, Gubina M, Brooks NJ, Zagaynova E, Kuimova MK, Shirmanova Met al., 2020, Mapping cisplatin-induced viscosity alterations in cancer cells using molecular rotor and fluorescence lifetime imaging microscopy, Journal of Biomedical Optics, Vol: 25, Pages: 1-16, ISSN: 1083-3668

Significance: Despite the importance of the cell membrane in regulation of drug activity, the influence of drug treatments on its physical properties is still poorly understood. The combination of fluorescence lifetime imaging microscopy (FLIM) with specific viscosity-sensitive fluorescent molecular rotors allows the quantification of membrane viscosity with high spatiotemporal resolution, down to the individual cell organelles.Aim: The aim of our work was to analyze microviscosity of the plasma membrane of living cancer cells during chemotherapy with cisplatin using FLIM and correlate the observed changes with lipid composition and cell’s response to treatment.Approach: FLIM together with viscosity-sensitive boron dipyrromethene-based fluorescent molecular rotor was used to map the fluidity of the cell’s membrane. Chemical analysis of membrane lipid composition was performed with time-of-flight secondary ion mass spectrometry (ToF-SIMS).Results: We detected a significant steady increase in membrane viscosity in viable cancer cells, both in cell monolayers and tumor spheroids, upon prolonged treatment with cisplatin, as well as in cisplatin-adapted cell line. ToF-SIMS revealed correlative changes in lipid profile of cisplatin-treated cells.Conclusions: These results suggest an involvement of membrane viscosity in the cell adaptation to the drug and in the acquisition of drug resistance.

Journal article

Carter JW, Gonzalez MA, Brooks NJ, Seddon JM, Bresme Fet 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.

Journal article

Mann SK, Devgan MK, Franks WT, Huband S, Chan CL, Griffith J, Pugh D, Brooks NJ, Welton T, Pham TN, McQueen LL, Lewandowski JR, Brown SPet al., 2020, MAS NMR Investigation of Molecular Order in an Ionic Liquid Crystal, JOURNAL OF PHYSICAL CHEMISTRY B, Vol: 124, Pages: 4975-4988, ISSN: 1520-6106

Journal article

Barriga H, Ces O, Law R, Seddon J, Brooks Net 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.

Journal article

Salvador Castell M, Brooks N, Peters J, Oger Pet al., 2019, Induction of non-lamellar phases in archaeal lipids at high temperature and high hydrostatic pressure by apolar polyisoprenoids, BBA: Biomembranes, ISSN: 0005-2736

It is now well established that cell membranes are much more than a barrier that separate the cytoplasm from the outside world. Regarding membrane’s lipids and their self-assembling, the system is highly complex, for example, the cell membrane needs to adopt different curvatures to be functional. This is possible thanks to the presence of non-lamellar-forming lipids, which tend to curve the membrane. Here, we present the effect of squalane, an apolar isoprenoid molecule, on an archaea-like lipid membrane. The presence of this molecule provokes negative membrane curvature and forces lipids to self-assemble under inverted cubic and inverted hexagonal phases. Such non-lamellar phases are highly stable under a broad range of external extreme conditions, e.g. temperatures and high hydrostatic pressures, confirming that such apolar lipids could be included in the architecture of membranes arising from cells living under extreme environments.

Journal article

Tyler AII, Greenfield JL, Seddon JM, Brooks NJ, Purushothaman Set 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

Journal article

Perez MP, Kuimova MK, Brooks NJ, 2019, Reorganization of liquid ordered lipid domains dampens changes in membrane tension, Joint 12th EBSA European Biophysics Congress / 10th IUPAP International Conference on Biological Physics (ICBP), Publisher: SPRINGER, Pages: S232-S232, ISSN: 0175-7571

Conference paper

Woodcock EM, Girvan P, Eckert J, Lopez-Duarte I, Kubankova M, van Loon JJWA, Brooks NJ, Kuimova MKet al., 2019, Measuring Intracellular Viscosity in Conditions of Hypergravity, BIOPHYSICAL JOURNAL, Vol: 116, Pages: 1984-1993, ISSN: 0006-3495

Journal article

Weber CC, Brooks NJ, Castiglione F, Mauri M, Simonutti R, Mele A, Welton Tet al., 2019, On the structural origin of free volume in 1-alkyl-3-methylimidazolium ionic liquid mixtures: a SAXS and 129Xe NMR study., Physical Chemistry Chemical Physics, Vol: 21, Pages: 5999-6010, ISSN: 1463-9076

Ionic liquid (IL) mixtures enable the design of fluids with finely tuned structural and physicochemical properties for myriad applications. In order to rationally develop and design IL mixtures with the desired properties, a thorough understanding of the structural origins of their physicochemical properties and the thermodynamics of mixing needs to be developed. To elucidate the structural origins of the excess molar volume within IL mixtures containing ions with different alkyl chain lengths, 3 IL mixtures containing 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ILs have been explored in a joint small angle X-ray scattering (SAXS) and 129Xe NMR study. The apolar domains of the IL mixtures were shown to possess similar dimensions to the largest alkyl chain of the mixture with the size evolution determined by whether the shorter alkyl chain was able to interact with the apolar domain. 129Xe NMR results illustrated that the origin of excess molar volume in these mixtures was due to fluctuations within these apolar domains arising from alkyl chain mismatch, with the formation of a greater number of smaller voids within the IL structure. These results indicate that free volume effects for these types of mixtures can be predicted from simple considerations of IL structure and that the structural basis for the formation of excess molar volume in these mixtures is substantially different to IL mixtures formed of different types of ions.

Journal article

Khan H, Seddon JM, Law RV, Brooks NJ, Robles E, Cabral JT, Ces Oet 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.

Journal article

Girvan P, Teng X, Brooks NJ, Baldwin GS, Ying Let al., 2019, Redox Kinetics of the Amyloid-Beta-Copper Complex and Its Biological Implications, 63rd Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 28A-28A, ISSN: 0006-3495

Conference paper

Brady RA, Kaufhold WT, Brooks NJ, Fodera V, Di Michele Let al., 2019, Flexibility defines structure in crystals of amphiphilic DNA nanostars, JOURNAL OF PHYSICS-CONDENSED MATTER, Vol: 31, ISSN: 0953-8984

Journal article

Menny A, Serna M, Boyd C, Gardner S, Joseph AP, Morgan BP, Topf M, Brooks NJ, Bubeck Det al., 2018, CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers, Nature Communications, Vol: 9, ISSN: 2041-1723

The membrane attack complex (MAC) is one of the immune system’s first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant β-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how β-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions.

Journal article

Trantidou T, Friddin M, Gan KB, Han L, Bolognesi G, Brooks N, Ces Oet al., 2018, Mask-free laser lithography for rapid and low-cost microfluidic device fabrication, Analytical Chemistry, Vol: 90, Pages: 13915-13921, ISSN: 0003-2700

Microfluidics has become recognized as a powerful platform technology associated with a constantly increasing array of applications across the life sciences. This surge of interest over recent years has led to an increased demand for microfluidic chips, resulting in more time being spent in the cleanroom fabricating devices using soft lithography—a slow and expensive process that requires extensive materials, training and significant engineering resources. This bottleneck limits platform complexity as a byproduct of lengthy delays between device iterations and affects the time spent developing the final application. To address this problem, we report a new, rapid, and economical approach to microfluidic device fabrication using dry resist films to laminate laser cut sheets of acrylic. We term our method laser lithography and show that our technique can be used to engineer 200 μm width channels for assembling droplet generators capable of generating monodisperse water droplets in oil and micromixers designed to sustain chemical reactions. Our devices offer high transparency, negligible device to device variation, and low X-ray background scattering, demonstrating their suitability for real-time X-ray-based characterization applications. Our approach also requires minimal materials and apparatus, is cleanroom free, and at a cost of around $1.00 per chip could significantly democratize device fabrication, thereby increasing the interdisciplinary accessibility of microfluidics.

Journal article

Brady RA, Brooks NJ, Foderà V, Cicuta P, Di Michele Let al., 2018, Amphiphilic-DNA platform for the design of crystalline frameworks with programmable structure and functionality, Journal of the American Chemical Society, Vol: 140, Pages: 15384-15392, ISSN: 1520-5126

The reliable preparation of functional, ordered, nanostructured frameworks would be a game changer for many emerging technologies, from energy storage to nanomedicine. Underpinned by the excellent molecular recognition of nucleic acids, along with their facile synthesis and breadth of available functionalizations, DNA nanotechnology is widely acknowledged as a prime route for the rational design of nanostructured materials. Yet, the preparation of crystalline DNA frameworks with programmable structure and functionality remains a challenge. Here we demonstrate the potential of simple amphiphilic DNA motifs, dubbed "C-stars", as a versatile platform for the design of programmable DNA crystals. In contrast to all-DNA materials, in which structure depends on the precise molecular details of individual building blocks, the self-assembly of C-stars is controlled uniquely by their topology and symmetry. Exploiting this robust self-assembly principle, we design a range of topologically identical, but structurally and chemically distinct C-stars that following a one-pot reaction self-assemble into highly porous, functional, crystalline frameworks. Simple design variations allow us to fine-tune the lattice parameter and thus control the partitioning of macromolecules within the frameworks, embed responsive motifs that can induce isothermal disassembly, and include chemical moieties to capture target proteins specifically and reversibly.

Journal article

Miller RM, Cabral J, Robles E, Brooks N, Ces Oet al., 2018, Crystallisation of sodium dodecyl sulfate–water micellar solutions with structurally similar additives: counterion variation, CrystEngComm, Vol: 20, Pages: 6834-6843, ISSN: 1466-8033

The effects of a series of structurally similar sodium dodecyl sulfate (SDS) additives on the crystallisation of SDS–water micellar solutions were investigated using a combination of differential scanning calorimetry, dynamic light scattering, optical microscopy and inductively coupled plasma optical emission spectroscopy. Seven different counterions were chosen from groups 1 and 2 of the periodic table to replace the sodium on SDS: LDS, (SDS), KDS, RbDS, CsDS, Mg(DS)2, Ca(DS)2 and Sr(DS)2. Two representative temperature profileswere employed – linear cooling ramps at rate of 0.5 °C min−1 to determine near-equilibrium kinetics and transitions and isothermal holds at 6 °C to elucidate morphological changes. Crystallisation of the reference solution 20% SDS–H2O with 0.25, 1.0 and 2.5% additive was generally promoted or inhibited even at the lowest concentrations. Melting points however remained largely unchanged, suggesting that the additives predominantly had a kinetic rather than thermodynamic effect. ICP-OES measurements for the solutions containing 1% additive indicated that most of the additives were integrated into the SDS crystals which was reflected by morphological changes, including the formation of hexagonal and oval shaped crystals. Our results both quantify and provide a morphological insight into the effect of a series of additives on the crystallisation of micellar SDS solutions, which can readily form due to preferential Na exchange.

Journal article

Barlow N, Kusumaatmaja H, Salehi-Reyhani A, Brooks N, Barter LMC, Flemming AJ, Ces Oet al., 2018, Measuring bilayer surface energy and curvature in asymmetric droplet interface bilayers, Journal of the Royal Society Interface, Vol: 15, ISSN: 1742-5662

For the past decade, droplet interface bilayers (DIBs) have had an increased prevalence in biomolecular and biophysical literature. However, much of the underlying physics of these platforms is poorly characterized. To further our understanding of these structures, lipid membrane tension on DIB membranes is measured by analysing the equilibrium shape of asymmetric DIBs. To this end, the morphology of DIBs is explored for the first time using confocal laser scanning fluorescence microscopy. The experimental results confirm that, in accordance with theory, the bilayer interface of a volume-asymmetric DIB is curved towards the smaller droplet and a lipid-asymmetric DIB is curved towards the droplet with the higher monolayer surface tension. Moreover, the DIB shape can be exploited to measure complex bilayer surface energies. In this study, the bilayer surface energy of DIBs composed of lipid mixtures of phosphatidylgylcerol (PG) and phosphatidylcholine are shown to increase linearly with PG concentrations up to 25%. The assumption that DIB bilayer area can be geometrically approximated as a spherical cap base is also tested, and it is discovered that the bilayer curvature is negligible for most practical symmetric or asymmetric DIB systems with respect to bilayer area.

Journal article

Girvan P, Teng X, Brooks NJ, Baldwin GS, Ying Let al., 2018, Redox Kinetics of the Amyloid-β-Cu Complex and Its Biological Implications, BIOCHEMISTRY, Vol: 57, Pages: 6228-6233, ISSN: 0006-2960

Journal article

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