polymer nanovesicles; switchable transport; engineered channel proteins; block copolymers
Alexandru Zabara, Renatta Negrini, Patric Bauman, Ozana Fischer, Raffaele Mezzenga (2014), Reconstitution of OmpF membrane protein on bended lipid bilayers: perforated hexagonal mesophases., in Chemical Communication
, 50(20), 2642-2645.
Baumman Patric, Fischer-Onaca Ozana, Balasubramanian Vimalkumar, Sienkiewicz Andrej, Palivan Cornelia (2013), Light-responsive polymer nanoreactors: a source of reactive oxygen species on demand, in Nanoscale
, 5, 217-224.
Onaca-Fischer Ozana, Lui Juan, Inglin Mark, Palivan Cornelia (2012), Polymeric Nanocarriers and Nanoreactors: A Survey of Possible Therapeutic Applications, in Current Pharmaceutical Design
, 18(18), 2622-2643.
Pascal Tanner, Stefan Egli, Vimalkumar Balasubramanian, Ozana Onaca, Cornelia Palivan, Wolfgang Meier (2011), Can polymeric vesicles that confine enzymatic reactions act as simplified organelles?, in FEBS Letters
, 585(11), 1699-1706.
Pascal Tanner, Patric Baumann, Ramona Enea, Ozana Onaca-Fischer, Cornelia Palivan, Wolfgang Meier (2011), Polymeric vesicles: From Drug Carriers to Nanoreactors and Artificial Organelles, in Accounts of Chemical Research
, 44(10), 1039-1049.
Cornelia Palivan, Ozana Fischer-Onaca, Mihaela Delcea, Fabian Itel, Wolfgang Meier (2011), Protein–polymer nanoreactors for medical applications, in Chemical Society Reviews
, 41, 2800-2023.
Kasper Renggli, Patric Baumann, Karolina Langowska, Ozana Onaca, Nico Bruns, Wolfgang Meier (2011), Selective and Responsive Nanoreactors, in Adv. Funct. Mater
, 21(7), 1241-1259.
Winna Siti, Hans-Peter Michael De Hoog, Ozana Onaca Fischer, Nikodem Tomczak, Yee Shan Wong, Madhavan Nallani, Bo Liedberg, Intercompartmental enzymatic cascade in channel-equipped polymersome-in-polymersome architectures, in J. Mater. Chem. B
Itel Fabian, Dinu Adrian, Tanner Pascal, Fischer Ozana, Palivan Cornelia, Nanoreactors for Biomedical Applications, in Torchilin Vladimir (ed.), World Scientific Publishing Co, Announced after publication.
Zabara Alexandru, Fischer-Onaca Ozana, Mezzenga Raffaele, Perforated Bicontinuous Cubic Phases with pH-Responsive Topological Channel Interconnectivity, in Small
Edlinger Christoph, Yang Xiaoyan, Fischer-Onaca Ozana, Palivan Cornelia, Polymer Nanoreactors, in Mihai Peterca (ed.), John Wiley and Sons, Inc, New Jersey.
In biological membranes channel proteins facilitate the transport of different molecules into and out of the cell. The transport of substances can be active transport or passive diffusion. Channel proteins like OmpF and Opdk which are found in the outer membrane of Escherichia coli and Pseudomonas aeruginosa, respectively, act as passive gateways for different small molecules (less than 600 Da). However in biological cell membranes they do not undergo conformational changes for increased selectivity in molecule transport.The aim of the project is to engineer channel proteins in order to obtain a reversible switchable transport across them. To achieve this, we plan to modify such unspecific channel proteins by introducing cysteines into the genes of the channels proteins. Responsive polymer chains that can respond to external stimuli such as temperature, light, pH, presence of ions, will be chemically attached to or grown from the introduced cysteines in order to constrict the channel. Upon appropriate exterior input, the polymer chain will change its solubility resulting in blockage of the channel pore, while restoring the initial conditions will cause the polymer to assume its earlier form of solubility and thus reopening the channel protein. By modulation of the polymer chain length it is possible to control the cutoff of the pore, transforming it in a molecular sieve for substances in certain molecular weight ranges. To the best of our knowledge, the approach for triggered transport across channel proteins would be the first of its kind for biological pores and will therefore offer a general strategy for obtaining reversible biological pores. Moreover we envisage that a blockage of the channel proteins with sensitive peptides (pH, temperature) introduced using genetic engineering methods will offer an alternative to the use of synthetic polymers for blocking.The reversibility of the switch introduced inside the channel proteins` pores will be characterized once the channel proteins are reconstituted in polymer nanovesicles. The polymeric nanovesicles are created by self assembly of amphiphilic block copolymers, for e.g poly-(2-methyloxazoline)-poly (dimethylsiloxane)-poly (2-methyloxazoline). The polymeric systems are a novel alternative to the liposome carriers, and are more stable, while preserving all the advantages of lipidic systems, such as lack of immunogenicity. The polymeric vesicles reconstituting engineered channel proteins will be characterized using fluorescence and spectroscopic methods. We anticipate that channel proteins engineered for reversible, controlled transport caused by changes in external stimulation (pH, temperature, light) will be used in drug delivery for tunable release of the content of liposomes or polymeric vesicles, as well as in biotechnological applications or biosensing.