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Membrane biophysics approaches to investigating the potential toxicity of engineered nanoparticles

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  • Full or part time
    Dr Beales
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

The purpose of this project is to study the interactions of synthetic nanoparticles with model biomembranes to understand the physical perturbations they cause to membrane structural properties and how these may lead to toxic responses in cells or advantageous properties for drug delivery.

New materials offer the prospect of exciting new technologies but also carry the risk of presenting new health hazards. One such class of new materials that presents exciting new technological prospects as well as considerable potential health risks are engineered nanomaterials.

This project will use advanced biophysical methods to investiagate the interactions of nanoparticles with reconstituted model biomembranes in the form of giant unilamellar vesicles (GUVs). GUVs are micro-scale, unsupported spherical lipid bilayers and hence have a similar structure to the membranes of natural cells. We will use optical microscopy techniques to monitor dynamic changes in membrane morphology (1,2), quantify changes in membrane permeability (3) and measure intra-membrane lipid dynamics in response to external nanoparticulate stimuli (4). We will assess how the response of these membranes depends upon their lipid composition, the physical properties of the nanoparticles and other physicochemical properties of the biomembrane’s environment (e.g. pH, salt concentration, presence of serum proteins, etc.) that impact upon the outcomes of these interactions.

In this way we aim to understand the detailed mechanisms by which these nanomaterials interact with biological membranes. This will reveal possible mechanisms for cellular uptake and/or damage, suggesting potentially nanoparticle toxicity or revealing auspicious properties that might be utilised in drug delivery applications or diagnostic imaging.

This multidisciplinary project will provide opportunities for the student to receive training in membrane biophysics, advanced optical imaging techniques and nano-characterisation.

Please contact Dr. Paul Beales ([email protected]) for further details about this opportunity.

Funding Notes

This research project is one of a number of projects at this institution. It is in competition for funding with one or more of these projects. Usually the project which receives the best applicant will be awarded the funding. Applications for this project are welcome from suitably qualified candidates worldwide. Funding may only be available to a limited set of nationalities and you should read the full department and project details for further information.

References

References:

(1) Beales P.A., Bergstrom C.L., Groves J.T. and Vanderlick T.K., Single Vesicle Observations of the Cardiolipin – Cytochrome c Interaction: Induction of Membrane Morphology Changes. Langmuir 27 (10), 6107-6115 (2011).

(2) Churchman A.H., Wallace R., Milne S.J., Brown A.P., Brydson R. and Beales P.A.; Serum Albumin enhances the Biomembrane Activity of ZnO Nanoparticles. Chem. Commun. 49 (39), 4172 - 4174 (2013).

(3) Bergstrom C.L., Beales P.A., Yang L., Vanderlick T.K. and Groves J.T.; Cytochrome c causes pore formation in cardiolipin-containing membranes. Proc. Natl. Acad. Sci. USA 110 (16), 6269 - 6274 (2013).

(4) Zhang S., Nelson L.A. and Beales P.A.; Freezing or wrapping, the role of particle size behind the mechanism of nanoparticle - biomembrane interaction. Langmuir 28 (35), 12831-12837 (2012).

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