Biomembrane interactions in the toxicology of nanoparticles to microorganisms

Lead Research Organisation: University of Leeds
Department Name: Centre for Molecular Nanoscience

Abstract

Nanoparticles and nanomaterials are having in increasing application in modern life. There are concerns however about their effect on the ecosystem and associated organisms and possible harmful effects directly and indirectly on human health. This is very important because the physics and chemistry of nanoparticles is rather anomalous. The size of nanoparticles means that their behaviour in aqueous systems lies somewhere in between dissolved and particulate species. This will also apply to their interaction with and possible accumulation by biological organisms. This proposal is a pilot study which attempts to address these issues. We propose to use two simple but well established, fundamental models to obtain a deeper understanding of the biological activity and bioaccumulation of nanoparticles and nanomaterials which are generally considered as safe. The objective of the study is to evaluate the mechanism of the biological response to the nanoparticles, the involvement of the cell membrane in the process and the relationship of the mechanism to the physical chemical characteristics of the nanoparticles in the culture meda. The classical membrane electrochemical model consisting of a phopholipid monolayer on a mercury electrode will be employed to evaluate the putative biomembrane activity of the nanoparticles. A bacterial bioassay method will be used with cultures of cyanobacteria to assess the biological activity and the bioaccumulation of the nanoparticles. Both series of experiments on the two models will be closely coordinated. The bulk of the study will be spent:(i) Characterising the nanoparticles with respect to their particle size, shape, surface charge, crystal structure and composition both initially and when added to culture medium with particular attention to their properties in dispersion, (ii)Studying the effects of the nanoparticles on a model biological membrane system, (iii) Studying the effects of the nanoparticles on the viability of cyanobacterial cultures. In these initial experiments both the electrochemical and bioassay experiments will be carried out in a buffered culture medium. The aim is to test the hypothesis that the biological membrane is critical in the mechanisms of toxicity of the nanoparticles At the end of the study we shall have developed a protocol based on this hypothesis for relating the biological activity of nanoparticles towards cyanobacteria to their physical and chemical functionality.

Publications

10 25 50

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Nelson A (2010) Electrochemistry of mercury supported phospholipid monolayers and bilayers in Current Opinion in Colloid & Interface Science

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Ringstad L (2008) An electrochemical study into the interaction between complement-derived peptides and DOPC mono- and bilayers. in Langmuir : the ACS journal of surfaces and colloids

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Sanver D (2016) Experimental Modeling of Flavonoid-Biomembrane Interactions. in Langmuir : the ACS journal of surfaces and colloids

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Vakurov A (2016) Significance of particle size and charge capacity in TiO2 nanoparticle-lipid interactions. in Journal of colloid and interface science

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Vakurov A (2012) Electrochemical modeling of the silica nanoparticle-biomembrane interaction. in Langmuir : the ACS journal of surfaces and colloids

 
Description The most significant findings of the project were the observation that SiO2 nanoparticles adsorbed on phospholipid membranes and that this was also observed for unicellular cyanobacteria. It was shown also that the supported membrane model of phospholipid layers on Hg electrode was a very effective relevant membrane model for screening the biomembrane activity of nanoparticle dispersions.
Exploitation Route The academic developments could be used to develop a commercial nanoparticle sensor for use in risk assessment of nanoparticle dispersions or water quality monitoring. The most effective exploitation route for these findings is to use the model membrane system as a first stage screener for the biomembrane activity of nanoparticle dispersions. This could be applied to the first stage screening of newly synthesised nanoparticles or to the screening of natural and potable waters for the presence of biomembrane active nanoparticles.
Sectors Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The findings laid the groundwork for the development and successful winning of an EU FP7 contract ENNSATOX in April 2009 with seven partners and Leeds as co-ordinator. The sensing system developed in the original NERC grant was at the heart of the EU project. The EU project enabled the sensing system to be ruggedised and critically validated against more conventional toxicity testing systems. At the same time the PI won the Brian Mercer Prize from the Royal Society proposing a commercialisation of the nanoparticle sensing technology developed during the NERC grant. The PI has licensed the technology to two successive companies but both these licensing operations have not been continued
First Year Of Impact 2009
Sector Environment,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Policy & public services

 
Description 2008 Royal Society Brian Mercer Award for Innovation in nanotechnology
Amount £187,000 (GBP)
Funding ID M 2008 R2 
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 01/2009 
End 12/2012
 
Description EU FP7 grant: Engineered Nanoparticle Impact on Aquatic Environments: Structure, Activity and Toxicology
Amount € 2,283,440 (EUR)
Funding ID NMP-229244 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 07/2009 
End 06/2012
 
Description NERC Pathfinder fund award
Amount £16,000 (GBP)
Funding ID NE/K001396/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 04/2012 
End 05/2012
 
Title Development of an an electrochemical screen for biomembrane active compounds and particles 
Description The screening platform consists of a membrane sensor element on mercury (Hg) microelectrode. The electrode is fabricated on a silicon wafer where the Hg is tightly bound to platinum (Pt). Biomembrane active compounds/particles interact with the membrane sensor element modifying its organisation in a specific and selective way. The technology now has a full performance evaluation and rivals any existing techniques for assaying biomembrane activity. The technology is also micronised and ruggedised to operate in a high throughput configuration. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Provided To Others? No  
Impact The most notable impact of this research has been the development of a collaboration with Unilever over the past year. The technology won Special Commendation by Lush Prize (2013) committee for services to the replacement of animals in testing 
 
Description Formation of EU consortium 
Organisation University of Wageningen
Country Netherlands 
Sector Academic/University 
PI Contribution An EU consortium was constructed of six partners from Netherlands, Belgium, Spain and Italy. Our experience derived from the grant enabled us to put together and lead this consortium and write a proposed work programme to widen and deepen the work carried out during the grant programme.
Start Year 2008
 
Description Regular talks to public on impact of science on society and impact of society on scientific work 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The talks have stimulated debate and discussion and instigated invitations to give further talks.

The talks gave rise to me developing novel university courses and to be invited to other universities to give talks on this subject ie scientific impact
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013