Periodical interacting networks will be designed by the application of graph theory establishing different geometries and topologies, in order to establish the construction rules and analyse the designs based on the concatenated interacting segments. Hexagonal as well as the tetragonal lattice will be constructed that will define the tightly knit lattice from the smallest number of different chains.
Research topics/Work packages within the MediSURF project
Membrane attachment of the polypeptide building blocks designed in WP1 will be achieved by chemical coupling of hydrophobic functional groups such as the acyl, phospholipid chains, sterols, transmembrane or membrane-insertion polypeptide domains. Single or multiple functional groups will be introduced at different positions (preferably terminal or at flexible linkers).
To study the structure of the MAPS in their native hydrated state they will be anchored to supported lipid bilayers on various substrates used, e.g. for cryo-TEM, highly transparent graphene oxide (GOox) sheets while for LP-TEM they will be immobilized on Si3N4 liquid cell windows. Cryo-TEM will provide high resolution in the lateral directions (task 3.1), whole liquid phase TEM will be used to study the dynamics of the system.
In Task 4.1, the biological activity of designed nanoparticles will be tested for the selectivity in cell targeting, cell entry, presentation of antigens, cell toxicity and activation of innate immune response. Tests will be performed on different cultured or primary human or mouse cells (e.g. THP-1, RAW, PBMCs, BMDMs, BMDCs,1 HEK203 transfected with different TLRs and cells deficient in different signalling pathways).