Experimental methods

Chemical synthesisCambridge, Leeds

Nano-objects synthesis and characterisation, polymer functionalisation

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    • Design, synthesis and characterization of biofunctional materials (e.g. stimuli-responsive polymers, functionalized nanoparticles, micelles and peptides) as generic non-viral vectors.
    • Formulation of specific drug delivery systems with integrated imaging, targeting and therapeutic functionalities for functional delivery of anticancer drugs and therapeutic proteins and nucleic acids. In-vitro and in-vivo testing in cell and tumor models for the treatment of specific diseases including cancers and cardiovascular diseases.
    • Investigation of extracellular and intracellular dynamics and mechanisms to optimize drug delivery systems.

Neutron experimentsManchester,Auckland

Neutron reflection and scattering

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    • Neutron reflection (NR) offers greater structural resolution, particularly with the help of deuterium labeling to lipid, solvent or lead molecule. Neutron reflection offers useful information about lateral structural morphology, e.g., large scale structural defects or undulations. NR can be applied to select systems where lead molecules show large affinity and selectivity to different membranes to determine the structural implications.

Microscopy techniquesStrasbourg, Cambridge, Swinburne

Optical microscopy, Transmission Electronic Microscopy

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    • Optical microscopy techniques: EPI and confocal fluorescence microscope (CFM) can be used for the 3D visualisations of domains and structures appearing in membranes of complex lipid composition, whether they belong to living cells or to artificial GUVs. CFM can track changes in lateral domains morphology following exposure to various nano-objects. CFM can localize them with wavelength precision, and the spatial resolution may be further improved if fluorescence energy transfer (FRET) conditions can be realised. Finally, CFM can probe membrane permeation during controlled released assays with encapsulating liposomes.
    • Transmission Electronic Microscopy (TEM) is the finest imaging method, and the only one that can display details smaller than the nanometre scale. CryoTEM combines the transmission electron microscopy mode with a fast freezing protocol of a thin water film containing the components of interest. CryoTEM can be used for probing membrane alterations consecutive to exposure to various external agents, inducing membrane thickening, budding, invagination or destabilisation with promising perspectives regarding the dynamics of these structural changes.

Biophysical methodsCopenhagen

Calorimetry, Electrophysiology

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    • Electrophysiological experiments on biological membranes aiming to detect and characterize the pores in the membranes arising spontaneously or induced by incorporated nano-objects.
    • Isothermal calorimetry (ITC) enables the determination of thermodynamical interactions between hydrated lipids and interacting molecules.
    • Fine studies of supported single and double bilayers prepared with the Langmuir-Blodgett and Langmuir-Schaeffer deposition techniques by AFM, X-ray and link to neutron reflectivity techniques.
    • We have local access to some common characterization techniques such as Mass Spectroscopy, Fluorescence Spectroscopy, Dynamic Light Scattering and NMR.

Biological methodsCambridge, Mainz, Leeds, Hangzhou

Tissue engineering, Drug delivery systems, Biostabilisation methods, Freeze-drying methods

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    • The network has skills in biomaterials synthesis and characterisation as well as in cell culture and the in-vitro characterisation of drug delivery systems. In vitro human cell culture models of these cell types can be used to determine the attachment, uptake, intracellular location in cells or translocation across the cells.

Theoretical methods

Molecular DynamicsDresden

Jens-Uwe Sommer

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    • Coarse grained Molecular Dynamics (MD) the LAMMPS package is a most flexible simulation method that gives access to the dynamics of the process of association of polymers and nano-objects with membranes at the molecular level. This technique is applied to study flexible and rigid objects (nano-rods, nano-particles) interacting with phospholipid bilayers.

Monte Carlo simulationsDresden

Jens-Uwe Sommer

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    • The Bond Fluctuation Model (BFM) is a fast algorithm to study the static and dynamic properties of polymers. The Dresden group has ample experience in developing BFM-code including the implementation on graphic processors (GPU) to speed up the calculations. This method is useful to study polymer – membrane interactions at larger scales than MD. For example, it can model the permeability of phospholipid bilayers upon the adsorption of polymers.

Analytical theory and scaling methodsDresden, Tarragona

Mean field and scaling theory calculations

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    • Mean field and scaling arguments can be used to describe global properties on large scales and predict adsorption of polymers on membranes

Single Chain Mean Field TheoryTarragona

Equilibrium properties of self-assembled systems

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    • The Single Chain Mean Field theory gives direct access to the equilibrium free energy which is hardly accessible by other simulation techniques, in particular, the energy of insertion of nanoparticles and CNTs into lipid bilayers. It is applied to study the equilibrium structures of synthesized polymers and nano-objects with membranes.
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