Objectif
The project focuses on developing voltage-sensitive nano-transducers (VSNs) suitable for long-term monitoring of neuronal membrane-potential. The proposed sensing technology seeks to empower the development of treatments against neurodegenerative pathologies, such as Alzheimer's, currently hampered by the photo-bleaching and photodynamic damage associated with conventional voltage-sensitive dyes (VSD). VSNs will exploit the novel concept of electrically tuneable plasmon resonant nano-particles/nano-rods (NP /NRs), nano-sensors that experience plasmon resonance shifts induced by the electric fields sub serving neuronal activation. To this end, a family of capping mono-layers endowed with conformational sensitivity to neuronal electric fields will be engineered by construction of chain-ball sensing arms including charged groups and flexible tethering alkyl chains. Other types of NP/NR-neuron interaction will also be studied as enhancers of voltage-sensitivity, including NP/NR-enabled monitoring of membrane nano-displacements (e.g. cellular swelling), variations of membrane refractive index and local heat production accompanying electrical activity. Transient changes in intensity, wavelength and phase of scattered light from neuron-bound NP/NRs will be studied using dark-field and phase sensitive microscopy combined with ultrahigh dynamic range active pixel sensors. NP/NRs of various sizes, shapes and compositions will be synthesised with a range of tether lengths and charged units. VSNs will be studied when bound to supported lipid bilayers, cultured neurons in isolation and cortical slices by simultaneous electrical control of dual layer and neuronal membrane potential and optical imaging/spectroscopy. To support the development and exploitation of the VSN technology, the optimal experimental setup will be integrated with the multi-electrode neurophysiology system developed and commercialised by one of the partners.
Champ scientifique
Appel à propositions
FP6-2004-NMP-TI-4
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