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Method for coating of solid phase substrates and lipid surfaces with a lattice-like clathrin structure

Reference Number TO 15-00241

Challenge

Coating of substrates allows an improvement of their mechanical, physical or chemical properties. Furthermore, surfaces can be functionalized which is of great importance in the biomedical field. Coating of medical devices can for example reduce immunogenicity and coating of liposomes could be used to improve their stability, enable specific binding to target structures or to generate vaccines. At the moment, mainly nanoparticles are used to functionalize surfaces. Therefore, there is a need for new technologies to functionalize surfaces in the pharmaceutical and cosmetics industry.

Top: Schematic cross section of carbon film coated with epsin and, thereon, the clathrin compounds forming the lattice- like structure. Bottom left: Negatively contrasted liposom coated with a flat clathrin lattice. Bottom right: negatively contrasted membrane buds, generated by coating the liposome surface with the epsin fragment and clathrin. Scale bar: 100 nm.
Top: Schematic cross section of carbon film coated with epsin and, thereon, the clathrin compounds forming the lattice- like structure. Bottom left: Negatively contrasted liposom coated with a flat clathrin lattice. Bottom right: negatively contrasted membrane buds, generated by coating the liposome surface with the epsin fragment and clathrin. Scale bar: 100 nm.

Technology

The present invention comprises an in vitro method to coat and functionalize the surface of both, solid phase substrates and lipid surfaces with a lattice-like clathrin structure. Clathrin, a protein found in all eukaryotic cells, is composed of three heavy and three light chains. The heavy chains form a stable trimer being recruited to membranes by the adaptor molecule epsin, thus supporting the formation of clathrin coated vesicles in vivo. The invented method refers to the use of modified epsin fragments to support a lattice-like clathrin coating. For liposomes this leads to an increase in stability and surface area due to periodical invaginations. Furthermore, clathrin light chains can be functionalized e.g. coupled to enzymes which are then positioned on the membrane in defined intervals thus allowing immobilization of liposomes to their target structures. In addition, clathrin-coated vesicles can be generated from invaginations of the liposomes allowing the generation of vaccines or an efficient and homogeneous packaging e.g. of pharmaceutical substances. The coating of solid phase substrates with a regular clathrin lattice could be used for many applications including reduction of immunogenicity of medical devices or as biotemplate for an inorganic catalyst. Furthermore, with a defined pore size of about 36 nm a flat clathrin lattice could be used as a molecular filter. Therefore, this technology has great potential for biological functionalization of surfaces with the advantage of a simple conjugation of biomolecules to the light chains of clathrin.

Commercial Opportunity

In-licensing or collaboration for further development is possible.

Developmental Status

Cell free system established for in vitro formation of clathrin-coated surfaces.

Patent Situation

European and US patent applications based on PCT/EP2013/052274 are pending

Further Reading

Dannhauser et al. 2015. Durable protein lattices of clathrin that can be functionalized with nanoparticles and actice biomolecules. Nat Nanotechnol. Nov;10(11):954-7.

Kelly et al. 2014. Clathrin adaptors. AP2 controls clathrin polimerization with a membrane-activated switch. Science. Jul 25;345(6195):459-63.

Dannhauser PN, Ungewickell EJ. 2012. Reconstitution of clathrin-coated bud and vesicle formation with minimal components. Nat Cel Biol. 14:634-639.