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Modelling basis and kinetics of nanoparticle interaction with membranes, uptake into cells, and sub-cellular and inter-compartmental transport

Objective

The prediction of biological (and in particular toxicological) impacts has, as its basic pre-requisite, the correct prediction of the sites of action and localization of the nanoparticle in living organisms. We have identified the need for a paradigm shift in modelling these properties for nanoscale objects. The interactions between bare particles and organisms (cells, biological barriers) is radically different in the presence of proteins and lipids derived from the biological environment (the ‘protein corona’). The bare particle characteristic is therefore insufficient to describe the system. Similarly, nanoparticles are trafficked and translocated between sites by active biological processes where traditional ‘equilibrium’ principles for small molecules no longer apply. NanoTransKinetics is firmly based on advanced high quality experimental data on the distribution of nanoparticles in cells, across barriers, and (more limited) in vivo. We frame phenomenological models in a modular manner by abstracting the essential relevant principles of particle-protein (and matrix) interactions, cellular and barrier transport mechanisms of nanoparticles, fitting them to experimental data. More detailed models allow for explicit checking of mechanisms and movements of individual particles into cells and across barriers. Enormous amounts of experimental data are now available to validate the models. A predictive capacity requires only simple input data on particle, corona and similar characteristics. The basis of these claims has been checked in preliminary studies, and a limited number of interactions, particles fluxes (and control parameters) between prescribed sites are sufficient to specify the system at each level of description. Resources (reaching far beyond the program itself) have been mobilised in experimental work in the Partners laboratories, and EU and US collaborations. The output will be predictive tools for use in nanosafety research and regulation and beyond.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/physical sciences/theoretical physics/particles
  • /social sciences/social and economic geography/transport

Call for proposal

FP7-NMP-2010-EU-USA
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Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Address
Belfield
4 Dublin
Ireland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 392 856
Administrative Contact
Donal Doolan (Mr.)

Participants (2)

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany
EU contribution
€ 314 400
Address
Geschwister Scholl Platz 1
80539 Muenchen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Joachim Raedler (Prof.)
UNIVERSITAT DE BARCELONA
Spain
EU contribution
€ 285 757
Address
Gran Via De Les Corts Catalanes 585
08007 Barcelona
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Xavier Gutierrez (Mr.)