ORCID Profile
0000-0002-2847-0253
Current Organisation
University of New South Wales
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Biochemistry and cell biology | Supramolecular chemistry | Synthetic biology |
Publisher: Wiley
Date: 07-12-2017
Abstract: Two peptide-derived low-molecular-weight gelators bearing different capping groups, 9-fluorenylmethyloxycarbonyl (Fmoc) and phenothiazine, were synthesized and their gel networks were characterized. The variation of the N-terminal capping group affects the viability of these hydrogels as a three-dimensional cell culture for multicellular tumor spheroids. These results indicate that the phenothiazine capping group is a more biocompatible alternative to the widely used Fmoc moiety.
Publisher: Cambridge University Press (CUP)
Date: 25-08-2021
DOI: 10.33774/CHEMRXIV-2021-02C1D
Abstract: Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors.
Publisher: Portland Press Ltd.
Date: 04-09-2019
DOI: 10.1042/ETLS20190094
Abstract: Cells, the discrete living systems that comprise all life on Earth, are a boundless source of inspiration and motivation for many researchers in the natural sciences. In the field of bottom-up synthetic cells, researchers seek to create multifaceted, self-assembled, chemical systems that mimic the properties and behaviours of natural life. In this perspective, we will describe the relatively recent application of complex coacervates to synthetic cells, and how they have been used to model an expanding range of biologically relevant phenomena. Furthermore, we will explore the unique advantages and disadvantages of coacervate-based synthetic cells, and their potential impact on the field in the years to come.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2020
DOI: 10.1038/S41467-020-20124-0
Abstract: The cell cytosol is crowded with high concentrations of many different biomacromolecules, which is difficult to mimic in bottom-up synthetic cell research and limits the functionality of existing protocellular platforms. There is thus a clear need for a general, biocompatible, and accessible tool to more accurately emulate this environment. Herein, we describe the development of a discrete, membrane-bound coacervate-based protocellular platform that utilizes the well-known binding motif between Ni 2+ -nitrilotriacetic acid and His-tagged proteins to exercise a high level of control over the loading of biologically relevant macromolecules. This platform can accrete proteins in a controlled, efficient, and benign manner, culminating in the enhancement of an encapsulated two-enzyme cascade and protease-mediated cargo secretion, highlighting the potency of this methodology. This versatile approach for programmed spatial organization of biologically relevant proteins expands the protocellular toolbox, and paves the way for the development of the next generation of complex yet well-regulated synthetic cells.
Publisher: American Chemical Society (ACS)
Date: 15-02-2021
Publisher: Wiley
Date: 15-09-2017
DOI: 10.1002/POLA.28780
Publisher: Wiley
Date: 26-02-2022
Abstract: The regulation of protein uptake and secretion is crucial for (inter)cellular signaling. Mimicking these molecular events is essential when engineering synthetic cellular systems. A first step towards achieving this goal is obtaining control over the uptake and release of proteins from synthetic cells in response to an external trigger. Herein, we have developed an artificial cell that sequesters and releases proteinaceous cargo upon addition of a coded chemical signal: single‐stranded DNA oligos (ssDNA) were employed to independently control the localization of a set of three different ssDNA‐modified proteins. The molecular coded signal allows for multiple iterations of triggered uptake and release, regulation of the amount and rate of protein release and the sequential release of the three different proteins. This signaling concept was furthermore used to directionally transfer a protein between two artificial cell populations, providing novel directions for engineering lifelike communication pathways inside higher order (proto)cellular structures.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4CC07941H
Abstract: A dipeptide bearing an indole capping group forms exceptionally strong, hydrogels, with a storage modulus of ∼0.3 MPa. these hydrogels exhibit a minimal fibre-branching, with strong lateral association of fibrils.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3OB40620B
Abstract: Ruthenium(II) and iridium(III) bis(terpyridine) complexes were prepared with maleimide functionalities in order to site-specifically modify yeast iso-1 cytochrome c possessing a single cysteine residue available for modification (CYS102). Single X-ray crystal structures were solved for aniline and maleimide Ru(II) 3 and Ru(II) 4, respectively, providing detailed structural detail of the complexes. Light-activated bioconjugates prepared from Ru(II) 4 in the presence of tris(2-carboxyethyl)-phosphine (TCEP) significantly improved yields from 6% to 27%. Photoinduced electron transfer studies of Ru(II)-cyt c in bulk solution and polymer membrane encapsulated specimens were performed using EDTA as a sacrificial electron donor. It was found that membrane encapsulation of Ru(II)-cyt c in PS140-b-PAA48 resulted in a quantum efficiency of 1.1 ± 0.3 × 10(-3), which was a two-fold increase relative to the bulk. Moreover, Ir(III)-cyt c bioconjugates showed a quantum efficiency of 3.8 ± 1.9 × 10(-1), equivalent to a ∼640-fold increase relative to bulk Ru(II)-cyt c.
Publisher: MyJove Corporation
Date: 20-07-2016
DOI: 10.3791/54157
Abstract: The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation. We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.
Publisher: MDPI AG
Date: 02-11-2020
Abstract: The careful design of nanoparticles, in terms of size and morphology, is of great importance to developing effective drug delivery systems. The ability to precisely tailor nanoparticles in size and morphology during polymer self-assembly was therefore investigated. Four poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) mPEG-b-p(HPMA-Bz) block copolymers with a fixed hydrophilic block of mPEG 5 kDa and a varying molecular weight of the hydrophobic p(HPMA-Bz) block (A: 17.1, B: 10.0, C: 5.2 and D: 2.7 kDa) were self-assembled into nanoparticles by nanoprecipitation under well-defined flow conditions, using microfluidics, at different concentrations. The nanoparticles from polymer A, increased in size from 55 to 90 nm using lower polymer concentrations and slower flow rates and even polymer vesicles were formed along with micelles. Similarly, nanoparticles from polymer D increased in size from 35 to 70 nm at slower flow rates and also formed vesicles along with micelles, regardless of the used concentration. Differently, polymers B and C mainly self-assembled into micelles at the different applied flow rates with negligible size difference. In conclusion, this study demonstrates that the self-assembly of mPEG-b-p(HPMA-Bz) block copolymers can be easily tailored in size and morphology using microfluidics and is therefore an attractive option for further scaled-up production activities.
Publisher: Elsevier
Date: 2021
Publisher: Wiley
Date: 25-07-2019
Abstract: In nature, dynamic processes are ubiquitous and often characterized by adaptive, transient behavior. Herein, we present the development of a transient bowl‐shaped nanoreactor system, or stomatocyte, the properties of which are mediated by molecular interactions. In a stepwise fashion, we couple motility to a dynamic process, which is maintained by transient events namely, binding and unbinding of adenosine triphosphate (ATP). The surface of the nanosystem is decorated with polylysine (PLL), and regulation is achieved by addition of ATP. The dynamic interaction between PLL and ATP leads to an increase in the hydrophobicity of the PLL–ATP complex and subsequently to a collapse of the polymer this causes a narrowing of the opening of the stomatocytes. The presence of the apyrase, which hydrolyzes ATP, leads to a decrease of the ATP concentration, decomplexation of PLL, and reopening of the stomatocyte. The competition between ATP input and consumption gives rise to a transient state that is controlled by the out‐of‐equilibrium process.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9CC08944F
Abstract: Here we report the shape transformation of poly(ethylene glycol)–polystyrene (PEG–PS) polymersomes into ordered inverse morphologies, directed by the salt concentration of the medium and the presence of azide groups on the polymersome surface.
Publisher: Wiley
Date: 26-02-2022
Abstract: The regulation of protein uptake and secretion is crucial for (inter)cellular signaling. Mimicking these molecular events is essential when engineering synthetic cellular systems. A first step towards achieving this goal is obtaining control over the uptake and release of proteins from synthetic cells in response to an external trigger. Herein, we have developed an artificial cell that sequesters and releases proteinaceous cargo upon addition of a coded chemical signal: single‐stranded DNA oligos (ssDNA) were employed to independently control the localization of a set of three different ssDNA‐modified proteins. The molecular coded signal allows for multiple iterations of triggered uptake and release, regulation of the amount and rate of protein release and the sequential release of the three different proteins. This signaling concept was furthermore used to directionally transfer a protein between two artificial cell populations, providing novel directions for engineering lifelike communication pathways inside higher order (proto)cellular structures.
Publisher: American Chemical Society (ACS)
Date: 05-2020
DOI: 10.1021/JACS.0C01732
Publisher: Springer Science and Business Media LLC
Date: 25-11-2021
DOI: 10.1038/S41467-021-27229-0
Abstract: Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors.
Publisher: American Chemical Society (ACS)
Date: 05-10-2016
DOI: 10.1021/ACSMACROLETT.6B00747
Abstract: One of the hallmarks of nature is compartmentalization, and natural cell membranes are often asymmetric in terms of the inner and outer side. This communication describes work toward synthesizing such an asymmetric membrane from the bottom-up. A family of hiphilic di- and triblock copolymers were synthesized via Cu(0)-mediated single electron transfer-living radical polymerization with the aim to generate polymer vesicles, or polymersomes, with an asymmetric membrane. Self-assembly of these polymeric hiphiles in aqueous media was investigated using asymmetric field-flow fractionation and cryo-electron microscopy. Utilizing mixtures of diblock copolymers with differing hydrophilic moieties resulted in the formation of vesicles with an asymmetric segregation of charge between the inner and outer leaflet, confirmed by zeta potential measurements. These polymers, synthesized in good yields and using a biologically compatible method to induce self-assembly, have a promising range of applications from nanomedicine to synthetic cell research.
Publisher: American Chemical Society (ACS)
Date: 17-11-2017
DOI: 10.1021/JACS.7B10846
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9NR06045F
Abstract: The core–shell architecture of biohybrid enzymes facilitates construction of multifunctional biofluids which display extremophilic traits in total absence of solvent.
Publisher: The Royal Society
Date: 17-08-2018
Abstract: Despite the astonishing ersity and complexity of living systems, they all share five common hallmarks: compartmentalization, growth and ision, information processing, energy transduction and adaptability. In this review, we give not only ex les of how cells satisfy these requirements for life and the ways in which it is possible to emulate these characteristics in engineered platforms, but also the gaps that remain to be bridged. The bottom-up synthesis of life-like systems continues to be driven forward by the advent of new technologies, by the discovery of biological phenomena through their transplantation to experimentally simpler constructs and by providing insights into one of the oldest questions posed by mankind, the origin of life on Earth.
Publisher: Wiley
Date: 25-07-2019
Publisher: Springer Science and Business Media LLC
Date: 29-09-2017
DOI: 10.1038/S41467-017-01372-Z
Abstract: Polymersomes, made up of hiphilic block copolymers, are emerging as a powerful tool in drug delivery and synthetic biology due to their high stability, chemical versatility, and surface modifiability. The full potential of polymersomes, however, has been hindered by a lack of versatile methods for shape control. Here we show that a range of non-spherical polymersome morphologies with anisotropic membranes can be obtained by exploiting hydrophobic directional aromatic interactions between perylene polymer units within the membrane structure. By controlling the extent of solvation/desolvation of the aromatic side chains through changes in solvent quality, we demonstrate facile access to polymersomes that are either ellipsoidal or tubular-shaped. Our results indicate that perylene aromatic interactions have a great potential in the design of non-spherical polymersomes and other structurally complex self-assembled polymer structures.
Publisher: American Chemical Society (ACS)
Date: 03-07-2019
Publisher: Wiley
Date: 29-05-2021
Abstract: Bottom‐up synthetic cells, where erse non‐living materials are combined in creative ways in order to construct increasingly life‐like and adaptive systems, are fast approaching a level of function that will enable significant advances in solving specific biomedical challenges. Over the last 10 years, we have seen a wide variety of synthetic cell based approaches to challenges in regulating antimicrobial activity, delivering cargo to mammalian cells, and “growth support”. Despite this progress, there has not been a widespread uptake of synthetic cell technologies in biomedical engineering. In this Review, we highlight both the strengths and limitations of these existing synthetic cell applications, as well as give an overview of the state‐of‐the‐art of synthetic cell technology that has yet been applied to cellular contexts. In doing so we aim to identify opportunities for the advancement of this unique intersection of research fields.
Publisher: Wiley
Date: 02-2021
DOI: 10.1002/POL.20200871
Abstract: Polymersomes have gained much interest within the biomedical field as drug delivery systems due to their ability to transport and protect cargo from the harsh environment inside the body. For an improved drug efficacy, control over cargo release is however also an important factor to take into account. An often employed method is to incorporate pH sensitive groups in the vesicle membrane, which induce disassembly and content release when the particles have reached a target site in the body with the appropriate pH, such as the acidic microenvironment of tumor tissue or the endosome. In this paper, biodegradable poly(ethylene glycol)‐poly(caprolactone‐ gradient ‐trimethylene carbonate)‐based polymeric vesicles have been developed with disassembly features at mild acidic conditions. Modifying the polymer backbone with imidazole moieties results in vesicle disassembly upon protonation due to the lowered pH. Furthermore, upon increasing the pH efficient re‐assembly into vesicles is observed due to the switchable hiphilic nature of the polymer. When this re‐assembly process is conducted in presence of cargo, enhanced encapsulation is achieved. Furthermore, the potency of the polymeric system for future biomedical applications such as adjuvant delivery is demonstrated.
Publisher: American Chemical Society (ACS)
Date: 28-06-2018
Start Date: 10-2023
End Date: 08-2027
Amount: $433,654.00
Funder: Australian Research Council
View Funded Activity