Publications
20 results found
Allen 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: 0027-8424
Artificial 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.
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.
Acosta-Gutierrez S, Matias D, Avila-Olias M, et al., 2022, A multiscale study of phosphorylcholine driven cellular phenotypic targeting, ACS Central Science, Vol: 8, ISSN: 2374-7943
Phenotypic targeting requires the ability of the drug delivery system to discriminate over cell populations expressing a particular receptor combination. Such selectivity control can be achieved using multiplexed-multivalent carriers often decorated with multiple ligands. Here, we demonstrate that the promiscuity of a single ligand can be leveraged to create multiplexed-multivalent carriers achieving phenotypic targeting. We show how the cellular uptake of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacry-late) (PMPC-PDPA) polymersomes varies depending on the receptor expression among different cells. We investigate the PMPC–PDPA polymersome insertion at the single chain/receptor level using all-atom molecular modeling. We propose a theoretical statistical mechanics-based model for polymersome–cell association that explicitly considers the interaction of the polymersome with the cell glycocalyx shedding light on its effect on the polymersome binding. We validate our model experimentally and show that the binding energy is a nonlinear function, allowing us to tune the interaction by varying the radius and degree of polymerization. Finally, we show that PMPC–PDPA polymersomes can be used to target monocytes in vivo due to their promiscuous interaction with SRB1, CD36, and CD81.
Contini C, Hu W, Elani Y, 2022, Manufacturing polymeric porous capsules, Chemical Communications, Vol: 58, Pages: 4409-4419, ISSN: 1359-7345
Polymeric 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.
Walczak M, Brady RA, Mancini L, et al., 2021, Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment, Nature Communications, Vol: 12, Pages: 1-11, ISSN: 2041-1723
Biology has evolved a variety of agents capable of permeabilising and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associatedwith disease or toxicity, these agents are also central to many biosensing and therapeutic tech nologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. We show that the corona can be selectively displaced with a molecu19 lar cue, exposing the ‘sticky’ core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria.
Zhang X, Contini C, Constantinou A, et al., 2021, How does the hydrophobic content of methacrylate ABA triblock copolymers affect polymersome formation?, Journal of Polymer Science, Vol: 59, Pages: 1724-1731, ISSN: 2642-4169
Polymersomes are exciting self-assembled structures with great potential in pharmaceutical applications. A systematic investigation of a novel series of methacrylate-based polymersomes is reported in this study. Five well-defined ABA triblock copolymers with A being based on tri(ethylene glycol) methyl methacrylate and B being based on 2-(diethylamino)ethyl methacrylate (DMAEMA) were synthesized using a living polymerization method. The effect of the composition of the ABA triblock copolymers on the thickness of the hydrophobic membrane of the polymersomes and the release of a model drug is demonstrated.
Zhang S, Contini C, Hindley J, et al., 2021, Engineering motile aqueous phase-separated droplets via liposome stabilisation, Nature Communications, Vol: 12, Pages: 1-11, ISSN: 2041-1723
There are increasing efforts to engineer functional compartments that mimic cellular behaviours from the bottom-up. One behaviour that is receiving particular attention is motility, due to its biotechnological potential and ubiquity in living systems. Many existing platforms make use of the Marangoni effect to achieve motion in water/oil (w/o) droplet systems. However, most of these systems are unsuitable for biological applications due to biocompatibility issues caused by the presence of oil phases. Here we report a biocompatible all aqueous (w/w) PEG/dextran Pickering-like emulsion system consisting of liposome-stabilised cell-sized droplets, where the stability can be easily tuned by adjusting liposome composition and concentration. We demonstrate that the compartments are capable of negative chemotaxis: these droplets can respond to a PEG/dextran polymer gradient through directional motion down to the gradient. The biocompatibility, motility and partitioning abilities of this droplet system offers new directions to pursue research in motion-related biological processes.
Kokot H, Kokot B, Sebastijanović A, et al., 2020, Prediction of chronic inflammation for inhaled particles: the impact of material cycling and quarantining in the lung epithelium, Advanced Materials, Vol: 32, ISSN: 0935-9648
On a daily basis, people are exposed to a multitude of health-hazardous airborne particulate matter with notable deposition in the fragile alveolar region of the lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modeling, it is determined herein that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows prediction of the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modeling, potentially relating outcomes to material properties for a large number of materials, and thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, this work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.
Scarpa E, De Pace C, Joseph AS, et al., 2020, Tuning cell behavior with nanoparticle shape, PLoS One, Vol: 15, Pages: 1-16, ISSN: 1932-6203
We investigated how the shape of polymeric vesicles, made by the exact same material, impacts the replication activity and metabolic state of both cancer and non-cancer cell types. First, we isolated discrete geometrical structures (spheres and tubes) from a heterogeneous sample using density-gradient centrifugation. Then, we characterized the cellular internalization and the kinetics of uptake of both types of polymersomes in different cell types (either cancer or non-cancer cells). We also investigated the cellular metabolic response as a function of the shape of the structures internalized and discovered that tubular vesicles induce a significant decrease in the replication activity of cancer cells compared to spherical vesicles. We related this effect to the significant up-regulation of the tumor suppressor genes p21 and p53 with a concomitant activation of caspase 3/7. Finally, we demonstrated that combining the intrinsic shape-dependent effects of tubes with the delivery of doxorubicin significantly increases the cytotoxicity of the system. Our results illustrate how the geometrical conformation of nanoparticles could impact cell behavior and how this could be tuned to create novel drug delivery systems tailored to specific biomedical application.
Contini C, Hindley J, Macdonald T, et al., 2020, Size dependency of gold nanoparticles interacting with model membranes, Communications Chemistry, Vol: 3, Pages: 1-12, ISSN: 2399-3669
The rapid development of nanotechnology has led to an increase in the number and variety of engineered nanomaterials in the environment. Gold nanoparticles (AuNPs) are an example of a commonly studied nanomaterial whose highly tailorable properties have generated significant interest through a wide range of research fields. In the present work, we characterise the AuNP-lipid membrane interaction by coupling qualitative data with quantitative measurements of the enthalpy change of interaction. We investigate the interactions between citrate-stabilised AuNPs ranging from 5 to 60 nm in diameter and large unilamellar vesicles acting as a model membrane system. Our results reveal the existence of two critical AuNP diameters which determine their fate when in contact with a lipid membrane. The results provide new insights into the size dependent interaction between AuNPs and lipid bilayers which is of direct relevance to nanotoxicology and to the design of NP vectors.
Zhang S, Contini C, Hindley J, et al., 2020, Engineering motile aqueous phase-separated droplets via liposome stabilisation
<jats:title>Abstract</jats:title> <jats:p>There are increasing efforts to engineer functional compartments that mimic aspects of cellular behaviour in a drive to construct an artificial cell from the bottom-up. One behaviour that is receiving particular attention is motility, due to its biotechnological potential and the fact that movement of discrete cells is a ubiquitous feature of living systems. Many existing platforms make use of the Marangoni effect to achieve motion in water/oil (w/o) droplet systems. However, most of these systems are unsuitable for biological applications due to issues with biocompatibility caused by the presence of oil phases. Here we report a biocompatible all aqueous (w/w) PEG/dextran Pickering-like emulsion system consisting of liposome-stabilized cell-sized droplets, where the stability can be easily tuned by adjusting liposome composition and concentration. We demonstrate that the compartments are capable of negative chemotaxis: if water is introduced into the emulsion system, these droplets can respond through directional motion away from PEG in the continuous phase and down to the polymer gradient with a velocity change proportional to the rearrangement of liposome stabilisers in the PEG/dextran interface. The biocompatibility, motility and partitioning abilities of this novel droplet system offers new directions to pursue research in motion-related biological processes.</jats:p>
Ambroz F, Xu W, Gadipelli S, et al., 2019, Room Temperature Synthesis of Phosphine-Capped Lead Bromide Perovskite Nanocrystals without Coordinating Solvents, PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION, Vol: 37, ISSN: 0934-0866
Contini C, Pearson R, Wang L, et al., 2018, Bottom-up evolution of vesicles from disks to high-genus polymersomes, iScience, Vol: 7, Pages: 132-144, ISSN: 2589-0042
Polymersomes are vesicles formed by the self-assembly of amphiphilic copolymers in water. They represent one of the most promising alternatives of natural vesicles as they add new possibilities in the amphiphiles' molecular engineering of aqueous compartments. Here we report the design of polymersomes using a bottom-up approach wherein self-assembly of amphiphilic copolymers poly(2-(methacryloyloxy) ethyl phosphorylcholine)-poly(2-(diisopropylamino) ethyl methacrylate) (PMPC-PDPA) into membranes is tuned using pH and temperature. We report evolution from disk micelles, to vesicles, to high-genus vesicles (vesicles with many holes), where each passage is controlled by pH switch or temperature. We show that the process can be rationalized, adapting membrane physics theories to disclose scaling principles that allow the estimation of minimal radius of vesiculation as well as chain entanglement and coupling. This approach allows us to generate nanoscale vesicles with genus from 0 to 70, which have been very elusive and difficult to control so far.
Macdonald TJ, Ambroz F, Batmunkh M, et al., 2018, TiO2 nanofiber photoelectrochemical cells loaded with sub-12 nm AuNPs: size dependent performance evaluation, Materials Today Energy, Vol: 9, Pages: 254-263, ISSN: 2468-6069
Incorporation of gold nanoparticles (AuNPs) into titanium dioxide (TiO2) photoelectrodes has been used traditionally to increase the performance of photoelectrochemical cells (PECs) through their tailored optical properties. In contrast to larger AuNPs, previous studies have suggested that smaller AuNPs are the most catalytic or effective at increasing the photovoltaic (PV) performance of TiO2 photoelectrodes based on PECs. Despite this, AuNPs are often only compared between sizes of 12–300 nm in diameter due to the most common synthesis, the Turkevich method, being best controlled in this region. However, the optimum radius for citrate-capped AuNPs sized between 5 and 12 nm, and their influence on the PV performances has not yet been investigated. In addition to using AuNPs in the photoelectrodes, replacing traditional TiO2 NPs with one-dimensional nanofibers (NFs) is a promising strategy to enhance the PV efficiency of the PECs due their capability to provide a direct pathway for charge transport. Herein, we exploit the advantages of two different nanostructured materials, TiO2 NFs and sub-12 nm AuNPs (5, 8, 10, and 12 nm), and fabricate composite based photoelectrodes to conduct a size dependent performance evaluation. The PECs assembled with 8 nm AuNPs showed ∼20% improvement in the average power conversion efficiency compared to the control PECs without AuNPs. The highest performing PEC achieved a power conversion efficiency of 8%, which to the best of our knowledge, is among the highest reported for scattering layers based on pure anatase TiO2 NFs. On the basis of our comprehensive investigations, we attribute this enhanced device performance using 8 nm AuNPs in the TiO2 NF photoelectrodes to the improved spectral absorption, decreased series resistance, and an increase in electron transport and injection rate leading to an increase in current density and fill factor.
Contini C, Schneemilch M, Gaisford S, et al., 2017, Nanoparticle–membrane interactions, Journal of Experimental Nanoscience, Vol: 13, Pages: 62-81, ISSN: 1745-8080
Engineered nanomaterials have a wide range of applications and as a result, are increasingly present in the environment. While they offer new technological opportunities, there is also the potential for adverse impact, in particular through possible toxicity. In this review, we discuss the current state of the art in the experimental characterisation of nanoparticle-membrane interactions relevant to the prediction of toxicity arising from disruption of biological systems. One key point of discussion is the urgent need for more quantitative studies of nano-bio interactions in experimental models of lipid system that mimic in vivo membranes.
Contini C, Joseph A, Cecchin D, et al., 2017, Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing, Science Advances, Vol: 3, ISSN: 2375-2548
In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred toas nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables theengineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the mostpromising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs,accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic,organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achievethis by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatibleasymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to anexternal gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremelysensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of thesenanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor–related protein 1) targeting, enables afourfold increase in penetration to the brain compared to nonchemotactic systems.
Ruiz-Perez L, Contini C, Battaglia G, 2017, Janus polymersomes, 253rd National Meeting of the American-Chemical-Society (ACS) on Advanced Materials, Technologies, Systems, and Processes, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
Robertson JD, Rizzello L, Avila-Olias M, et al., 2016, Purification of nanoparticles by size and shape, Scientific Reports, Vol: 6, ISSN: 2045-2322
Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions.
Roberts JJ, Best BD, Mannocci L, et al., 2016, Habitat-based cetacean density models for the US Atlantic and Gulf of Mexico, Scientific Reports, Vol: 6, ISSN: 2045-2322
Cetaceans are protected worldwide but vulnerable to incidental harm from an expanding array of human activities at sea. Managing potential hazards to these highly-mobile populations increasingly requires a detailed understanding of their seasonal distributions and habitats. Pursuant to the urgent need for this knowledge for the U.S. Atlantic and Gulf of Mexico, we integrated 23 years of aerial and shipboard cetacean surveys, linked them to environmental covariates obtained from remote sensing and ocean models, and built habitat-based density models for 26 species and 3 multi-species guilds using distance sampling methodology. In the Atlantic, for 11 well-known species, model predictions resembled seasonal movement patterns previously suggested in the literature. For these we produced monthly mean density maps. For lesser-known taxa, and in the Gulf of Mexico, where seasonal movements were less well described, we produced year-round mean density maps. The results revealed high regional differences in small delphinoid densities, confirmed the importance of the continental slope to large delphinoids and of canyons and seamounts to beaked and sperm whales, and quantified seasonal shifts in the densities of migratory baleen whales. The density maps, freely available online, are the first for these regions to be published in the peer-reviewed literature.
Cecchin D, Joseph A, Nyberg S, et al., 2014, Enzyme-driven chemotactic synthetic vesicles, 248th National Meeting of the American-Chemical-Society (ACS), Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
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