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Effect of nanoparticles on membrane fusion

Objective

Nanoparticles (NPs) of different sizes, shapes, materials, and surface chemistry have been increasingly incorporated in modern formulations. In these applications, it is ubiquitous that NPs are exposed to biological media and come into intimate contact with cells. There is currently an urgent need to bridge the gap in our knowledge of NP toxicity in order to fulfil the potential of nanomaterial application. Such an understanding is also critical to the public perception of the safety of nanomaterials. Gaining cellular entry is a major route for NPs to impart toxicity. Studies using cell viability assays provide useful phenomenological information on the toxicity of specific NPs against specific cells under specific conditions, which however gives limited mechanistic insights into how NP physical properties are correlated with their cellular entrance and consequent toxicity. Physicochemical experiments using quantitative methods to probe the fundamental process of NP cellular entrance are lacking. A directly relevant fundamental area on the mechanisms of NP cellular entrance but remains largely unexplored is how NPs would affect the mechanism of membrane fusion - specifically, how the presence of NPs may lower the energetic barrier in the membrane fusion process. The scientific innovation of this project is to directly measure, using the surface force apparatus (SFA), in situ and in real time, interactions and fusion between model membranes (i.e. supported lipid bilayers) in the presence of NPs and as a function of lipid compositions and physicochemical properties of NPs. Direct visualisation of membrane contact in the SFA allows the role of NPs in the spatiotemporal structural evolution of membrane fusion, as the membranes engage in contact, compression, adhesion and fusion. These measurements will lead to unprecedented results, shedding light on the fundamentals of NP-mediated membrane fusion, relevant to our understanding of how NP gain cellular entry.

Call for proposal

H2020-MSCA-IF-2020
See other projects for this call

Coordinator

UNIVERSITY OF BRISTOL
Address
Beacon House Queens Road
BS8 1QU Bristol
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 224 933,76