Mibel Aguilar

Exosome trapping and enrichment using a sound wave activated nano-sieve (SWANS)

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/D0LC00623H

Abstract: Mechanically activated packed-bed of beads (SWANS) traps and rapidly enriches the concentration of exosomes, a form of extracellular vesicles, while preserves the integrity of the lipid bilayer membrane. Also, larger beads perform better in capturing.

Exploring Molecular-Biomembrane Interactions with Surface Plasmon Resonance and Dual Polarization Interferometry Technology: Expanding the Spotlight onto Biomembrane Structure

Publisher: American Chemical Society (ACS)

Date: 25-05-2018

DOI: 10.1021/ACS.CHEMREV.7B00729

Abstract: The molecular analysis of biomolecular-membrane interactions is central to understanding most cellular systems but has emerged as a complex technical challenge given the complexities of membrane structure and composition across all living cells. We present a review of the application of surface plasmon resonance and dual polarization interferometry-based biosensors to the study of biomembrane-based systems using both planar mono- or bilayers or liposomes. We first describe the optical principals and instrumentation of surface plasmon resonance, including both linear and extraordinary transmission modes and dual polarization interferometry. We then describe the wide range of model membrane systems that have been developed for deposition on the chips surfaces that include planar, polymer cushioned, tethered bilayers, and liposomes. This is followed by a description of the different chemical immobilization or physisorption techniques. The application of this broad range of engineered membrane surfaces to biomolecular-membrane interactions is then overviewed and how the information obtained using these techniques enhance our molecular understanding of membrane-mediated peptide and protein function. We first discuss experiments where SPR alone has been used to characterize membrane binding and describe how these studies yielded novel insight into the molecular events associated with membrane interactions and how they provided a significant impetus to more recent studies that focus on coincident membrane structure changes during binding of peptides and proteins. We then discuss the emerging limitations of not monitoring the effects on membrane structure and how SPR data can be combined with DPI to provide significant new information on how a membrane responds to the binding of peptides and proteins.

Effects of Rationally Designed Physico-Chemical Variants of the Peptide PuroA on Biocidal Activity towards Bacterial and Mammalian Cells

Publisher: MDPI AG

Date: 16-11-2020

DOI: 10.3390/IJMS21228624

Abstract: Antimicrobial peptides (AMPs) often exhibit wide-spectrum activities and are considered ideal candidates for effectively controlling persistent and multidrug-resistant wound infections. PuroA, a synthetic peptide based on the tryptophan (Trp)-rich domain of the wheat protein puroindoline A, displays strong antimicrobial activities. In this work, a number of peptides were designed based on PuroA, varying in physico-chemical parameters of length, number of Trp residues, net charge, hydrophobicity or hipathicity, D-versus L-isomers of amino acids, cyclization or dimerization, and were tested for antimicrobial potency and salt and protease tolerance. Selected peptides were assessed for effects on biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and selected mammalian cells. Peptide P1, with the highest hipathicity, six Trp and a net charge of +7, showed strong antimicrobial activity and salt stability. Peptides W7, W8 and WW (seven to eight residues) were generally more active than PuroA and all diastereomers were protease-resistant. PuroA and certain variants significantly inhibited initial biomass attachment and eradicated preformed biofilms of MRSA. Further, P1 and dimeric PuroA were cytotoxic to HeLa cells. The work has led to peptides with biocidal effects on common human pathogens and/or anticancer potential, also offering great insights into the relationship between physico-chemical parameters and bioactivities, accelerating progress towards rational design of AMPs for therapeutics.

Elucidating the cell penetrating properties of self-assembling beta-peptides

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D3NR03673A

A switch in N-terminal capping of β-peptides creates novel self-assembled nanoparticles

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D3RA04514E

Identifying the Coiled-Coil Triple Helix Structure of β-Peptide Nanofibers at Atomic Resolution

Publisher: American Chemical Society (ACS)

Date: 29-08-2018

DOI: 10.1021/ACSNANO.8B03131

Abstract: Peptide self-assembly represents a powerful bottom-up approach to the fabrication of nanomaterials. β

Multi-Omic Analysis to Characterize Metabolic Adaptation of the E. coli Lipidome in Response to Environmental Stress

Publisher: MDPI AG

Date: 11-02-2022

DOI: 10.3390/METABO12020171

Abstract: As an adaptive survival response to exogenous stress, bacteria undergo dynamic remodelling of their lipid metabolism pathways to alter the composition of their cellular membranes. Here, using Escherichia coli as a well characterised model system, we report the development and application of a ‘multi-omics’ strategy for comprehensive quantitative analysis of the temporal changes in the lipidome and proteome profiles that occur under exponential growth phase versus stationary growth phase conditions i.e., nutrient depletion stress. Lipidome analysis performed using ‘shotgun’ direct infusion-based ultra-high resolution accurate mass spectrometry revealed a quantitative decrease in total lipid content under stationary growth phase conditions, along with a significant increase in the mol% composition of total cardiolipin, and an increase in ‘odd-numbered’ acyl-chain length containing glycerophospholipids. The inclusion of field asymmetry ion mobility spectrometry was shown to enable the enrichment and improved depth of coverage of low-abundance cardiolipins, while ultraviolet photodissociation-tandem mass spectrometry facilitated more complete lipid structural characterisation compared with conventional collision-induced dissociation, including unambiguous assignment of the odd-numbered acyl-chains as containing cyclopropyl modifications. Proteome analysis using data-dependent acquisition nano-liquid chromatography mass spectrometry and tandem mass spectrometry analysis identified 83% of the predicted E. coli lipid metabolism enzymes, which enabled the temporal dependence associated with the expression of key enzymes responsible for the observed adaptive lipid metabolism to be determined, including those involved in phospholipid metabolism (e.g., ClsB and Cfa), fatty acid synthesis (e.g., FabH) and degradation (e.g., FadA/B,D,E,I,J and M), and proteins involved in the oxidative stress response resulting from the generation of reactive oxygen species during β-oxidation or lipid degradation.

β³-Tripeptides Coassemble into Fluorescent Hydrogels for Serial Monitoring in Vivo

Publisher: American Chemical Society (ACS)

Date: 02-10-2018

DOI: 10.1021/ACSBIOMATERIALS.8B01065

Staphylococcus aureus entanglement in self-assembling beta-peptide nanofibres decorated with vancomycin

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D0NA01018A

Abstract: Peptides containing vancomycin were able to self-assemble into antimicrobial 2D scaffolds.

Esterase-Mediated Sustained Release of Peptide-Based Therapeutics from a Self-Assembled Injectable Hydrogel

Publisher: American Chemical Society (ACS)

Date: 10-11-2021

DOI: 10.1021/ACSAMI.1C14150

An Active Site Inhibitor Induces Conformational Penalties for ACE2 Recognition by the Spike Protein of SARS-CoV-2

Publisher: American Chemical Society (ACS)

Date: 03-03-2021

DOI: 10.1021/ACS.JPCB.0C11321

The impact of antibacterial peptides on bacterial lipid membranes depends on stage of growth.

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D0FD00052C

Abstract: The impact of maculatin 1.1 (Mac1) on the mechanical properties of supported lipid membranes derived from exponential growth phase (EGP) and stationary growth phase (SGP)

A comparison of fixation methods for SEM analysis of self-assembling peptide hydrogel nanoarchitecture

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D2NR04598B

Abstract: SEM preparation techniques for self-assembling peptide hydrogels can have dramatic influence on apparent structure.

Self-assembly of trifunctional tripeptides to form neural scaffolds

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D0TB02959A

Abstract: A trifunctionalised tripeptide monomer self-assembles to form scaffolds that support the growth and maintenance of functional primary neurons.

Using conformational constraints at position 6 of Angiotensin II to generate compounds with enhanced AT2R selectivity and proteolytic stability

Publisher: Elsevier BV

Date: 07-2021

DOI: 10.1016/J.BMCL.2021.128086

Comparison of reversible membrane destabilisation induced by antimicrobial peptides derived from Australian frogs

Publisher: Elsevier BV

Date: 09-2014

DOI: 10.1016/J.BBAMEM.2014.02.017

Abstract: The membrane destabilising properties of the antimicrobial peptides (AMP) aurein 1.2, citropin 1.1, maculatin 1.1 and caerin 1.1, have been studied by dual polarisation interferometry (DPI). The overall process of peptide induced membrane destabilisation was examined by the changes in bilayer order as a function of membrane-bound peptide mass per unit area and revealed three different modes of action. Aurein 1.2 was the only peptide that significantly destabilised the neutral membrane (DMPC), while all four peptides induced destabilisation of the negatively charged membrane (DMPC/DMPG). On DMPC, citropin 1.1, maculatin 1.1 and caerin 1.1 bound irreversibly at low concentrations but caused a reversible drop in the bilayer order. In contrast to DMPC/DMPG, these three peptides caused a mass drop at the higher concentrations, which may correspond to insertion and bilayer expansion. The critical level of bound peptide necessary to induce membrane destabilisation (peptide:lipid ratio) was determined and correlated with peptide structure. As the most lytic peptide, aurein 1.2 adsorbed strongly prior to dissolution of the bilayer. In contrast, the binding of citropin 1.1, maculatin 1.1 and caerin 1.1 needed to reach a critical level prior to insertion into the membrane and incremental expansion and disruption. Our results demonstrate that sequential events can be monitored in real-time under fluidic conditions to elucidate the complex molecular mechanism of AMP action. In particular, the analysis of birefringence in real time allows the description of a detailed mechanistic model of the impact of peptides on the membrane bilayer order. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

Self-assembling injectable peptide hydrogels for emerging treatment of ischemic stroke

Publisher: Royal Society of Chemistry (RSC)

Date: 2019

DOI: 10.1039/C9TB00257J

Abstract: Ischaemic stroke remains one of the leading causes of death and disability worldwide, without any long-term effective treatments targeted at regeneration. This has led to developments of novel, biomaterial-based strategies using self-assembling peptide hydrogels.

The protective effects of a novel AT2 receptor agonist, ?-Pro7Ang III in ischemia-reperfusion kidney injury

Publisher: Elsevier BV

Date: 05-2023

DOI: 10.1016/J.BIOPHA.2023.114556

Novel AT2R agonist, & beta;-Pro7Ang III, is cardio- and vaso-protective in diabetic spontaneously hypertensive rats

Publisher: Elsevier BV

Date: 09-2023

DOI: 10.1016/J.BIOPHA.2023.115238

The Novel AT2 Receptor Agonist β-Pro7-AngIII Exerts Cardiac and Renal Anti-Fibrotic and Anti-Inflammatory Effects in High Salt-Fed Mice

Publisher: MDPI AG

Date: 14-11-2022

DOI: 10.3390/IJMS232214039

Abstract: A high salt (HS) diet is associated with an increased risk for cardiovascular diseases (CVDs) and fibrosis is a key contributor to the organ dysfunction involved in CVDs. The activation of the renin angiotensin type 2 receptor (AT2R) has been considered as organ protective in many CVDs. However, there are limited AT2R-selective agonists available. Our first reported β-substituted angiotensin III peptide, β-Pro7-AngIII, showed high selectivity for the AT2R. In the current study, we examine the potential anti-fibrotic and anti-inflammatory effects of this novel AT2R-selective peptide on HS-induced organ damage. FVB/N mice fed with a 5% HS diet for 8 weeks developed cardiac and renal fibrosis and inflammation, which were associated with increased TGF-β1 levels in heart, kidney and plasma. Four weeks’ treatment (from weeks 5–8) with β-Pro7-AngIII inhibited the HS-induced cardiac and renal fibrosis and inflammation. These protective effects were accompanied by reduced local and systemic TGF-β1 as well as reduced cardiac myofibroblast differentiation. Importantly, the anti-fibrotic and anti-inflammatory effects caused by β-Pro7-AngIII were attenuated by the AT2R antagonist PD123319. These results demonstrate, for the first time, the cardio- and reno-protective roles of the AT2R-selective β-Pro7-AngIII, highlighting it as an important therapeutic that can target the AT2R to treat end-organ damage.

Biomaterial Strategies for Restorative Therapies in Parkinson's Disease

Publisher: American Chemical Society (ACS)

Date: 11-10-2021

DOI: 10.1021/ACSCHEMNEURO.1C00484

Discovery Projects - Grant ID: DP1093675

Start Date: 2010

End Date: 12-2012

Amount: $270,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP120200794

Start Date: 07-2013

End Date: 06-2015

Amount: $240,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0449980

Start Date: 04-2004

End Date: 12-2006

Amount: $240,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP190102290

Start Date: 04-2019

End Date: 04-2022

Amount: $500,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP110101866

Start Date: 2011

End Date: 12-2013

Amount: $310,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668017

Start Date: 2006

End Date: 12-2008

Amount: $1,047,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882977

Start Date: 09-2008

End Date: 12-2009

Amount: $600,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882913

Start Date: 05-2008

End Date: 12-2008

Amount: $300,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0883541

Start Date: 07-2008

End Date: 12-2010

Amount: $850,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0669856

Start Date: 12-2006

End Date: 06-2008

Amount: $671,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100068

Start Date: 2014

End Date: 09-2015

Amount: $280,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0557486

Start Date: 03-2005

End Date: 12-2007

Amount: $410,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100174

Start Date: 12-2011

End Date: 12-2012

Amount: $800,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0774893

Start Date: 06-2007

End Date: 06-2010

Amount: $210,000.00

Funder: Australian Research Council

Special Research Initiatives - Grant ID: SR0354583

Start Date: 06-2004

End Date: 12-2004

Amount: $10,000.00

Funder: Australian Research Council

Industrial Transformation Training Centres - Grant ID: IC190100026

Start Date: 01-2021

End Date: 11-2027

Amount: $4,969,663.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100096

Start Date: 2017

End Date: 10-2017

Amount: $325,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100036

Start Date: 2010

End Date: 12-2011

Amount: $470,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775692

Start Date: 07-2007

End Date: 12-2008

Amount: $430,000.00

Funder: Australian Research Council