A Basis for Molecular Factories: Multifunctionality and Immobilization of Biomolecule-Polymer Assemblies

  • Engineering Cellular Systems.
    Engineering Cellular Systems.

The ultimate goal of this project is to create complex networks of reactors/processors as a basis for molecular factories. Over the long term, it is anticipated that the organelles and model cells that we will design and develop will provide a new, theragnostic strategy, very much in demand today in the medical domain. In addition, molecular factories will be specifically designed to support applications in environmental science, food science and technology.

Polymer supramolecular structures in the form of micelles, vesicles, and films are of particular interest as building blocks/templates for molecular factories. If appropriately designed from the point of view of chemical nature and properties, these structures can favour the insertion/encapsulation/attachment of biological molecules that serve as active blocks without dramatically impairing their function.

Polymer vesicles and planar membranes selectively permit encapsulation of a variety of biomolecules, ranging from low molar mass components to functional enzymes and proteins, without hampering their activities. In addition, polymer membranes modified by the insertion of channel proteins allow for the selective exchange of molecular components/reaction products between the inside and outside of a membrane cavity, while the functionalization of their surfaces supports targeted approaches.

The approach differs from others in that, due to its chemical nature, the membrane itself is permeable by inserting channel proteins.

Initially, the variety of amphiphilic copolymers, and later the multifunctionality and responsiveness of biomolecule – polymer assemblies will be extended, by integrating them in complex networks that will support molecular factories.

 

Scientific Highlight

Nanoreactors against malaria (see link to article “Nanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites“ below): Polymer vesicles were designed by the two NCCR-Groups Meier and Palivan to present specific host cell receptors on their surface. Such nanoreactors mimick red blood cells, which are the target of Plasmodium falciparum parasites that cause malaria. When added to a parasite culture, these nanoreactors efficiently interrupt the life cycle of P. falciparum by rapidly binding to the surface of malaria parasites. This inhibits the invasion of uninfected red blood cells, thus efficiently terminating the malaria blood-stage cycle. This new patented strategy offers promising treatments for several severe diseases.

Articles

J. Gaitzsch, L. Messager, E. Morecroft, W. MeierVesicles in Multiple Shapes: Fine-Tuning Polymersomes’ Shape and Stability by Setting Membrane Hydrophobicity“ Polymers 9, 10, 483 (2017). [Link]
E. V. Konishcheva, U. E. Zhumaev, M. Kratt, V. Oehri, W. MeierComplex Self-Assembly Behavior of Bis-hydrophilic PEO-b-PCL-b-PMOXA Triblock Copolymers in Aqueous Solution“ Macromolecules (2017). [Link]
C. Edlinger, T. Einfalt, M. Spulber, A. CarW. MeierC. G. PalivanBiomimetic Strategy To Reversibly Trigger Functionality of Catalytic Nanocompartments by the Insertion of pH-Responsive Biovalves“ Nano Lett. (2017). [Link]
V. Mikhalevich, I. Craciun, M. Kyropoulou, C. G. PalivanW. MeierAmphiphilic peptide self-assembly: Expansion to hybrid materials“ Biomacromolecules (2017). [Link]
G. Gunkel-GraboleC. G. PalivanW. MeierNanostructured Surfaces through Immobilization of Self-Assembled Polymer Architectures Using Thiol–Ene Chemistry“ Macromol. Mater. Eng. 302, 1600363 (2017). [Link]
I. Craciun, G. Gunkel-Grabole, A. Belluati, C. G. PalivanW. MeierExpanding the potential of MRI contrast agents through multifunctional polymeric nanocarriers“ Nanomedicine 12, 811-17 (2017). [Link]
N. ChuardS. MatileW. MeierC. G. PalivanStrain-Promoted Thiol-Mediated Cellular Uptake of Giant Substrates: Liposomes and Polymersomes“ Angew. Chem. Int. Ed. 56, 2947-50 (2017). [Link]
P. Baumann, M. Spulber, O. Fischer, A. CarW. MeierInvestigation of Horseradish Peroxidase Kinetics in an “Organelle-Like” Environment“ Small 13, 1603943 (2017). [Link] [More Information]
J. Liu, V. Postupalenko, S. Lörcher, D. Wu, M. Chami, W. MeierC. G. PalivanDNA-Mediated Self-Organization of Polymeric Nanocompartments Leads to Interconnected Artificial Organelles“ Nano Lett., DOI: 10.1021/acs.nanolett.6b03430 (2016). [Link] [More Information]
D. Vasquez, T. Einfalt, W. MeierC. G. PalivanAsymmetric Triblock Copolymer Nanocarriers for Controlled Localization and pH-Sensitive Release of Proteins“ Langmuir 32, 10235-43 (2016). [Link]
S. J. Sigg, F. Santini, A. Najer, P. U. Richard, W. MeierC. G. PalivanNanoparticle-based highly sensitive MRI contrast agents with enhanced relaxivity in reductive milieu“ Chem. Commun. 52, 9937-40 (2016). [Link]
D. Harder, S. Hirschi, Z. Ucurum, R. Goers, W. MeierD. J. MüllerD. FotiadisEngineering a Chemical Switch into the Light-driven Proton Pump Proteorhodopsin by Cysteine Mutagenesis and Thiol Modification“ Angew. Chem. Int. Ed.  55, 8846 (2016). [Link]
A. Najer, D. Wu, M. G. Nussbaumer, G. Schwertz, A. Schwab, M. C. Witschel, A. Schäfer, F. Diederich, M. Rottmann, C. G. Palivan, H. Beck, W. MeierAn amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery“ Nanoscale, DOI: 10.1039/C6NR04290B (2016). [Link]
S. HirschiM. Stauffer, D. Harder, D. J. MüllerW. MeierD. FotiadisEngineering and Assembly of Protein Modules into Functional Molecular Systems“ Chimia 6, 398 (2016). [Link]
Y. CotelleN. Chuard, S. Lascano, V. Lebrun, R. Wehlauch, N. Bohni, S. Lörcher, V. Postupalenko, S. ReddyW. MeierC. G. PalivanK. GademannT. R. WardS. MatileInterfacing Functional Systems“ Chimia 6, 418 (2016). [Link]
C. E. HousecroftC. G. PalivanK. GademannW. MeierM. CalameV. Mikhalevich, X. Zhang, E. PielM. SzponarskiA. WieslerA. Lanzilotto, E. C. Constable, A. Fanget, R. Stoop “‘Active surfaces’ as Possible Functional Systems in Detection and Chemical (Bio) Reactivity“ Chimia 6, 402 (2016). [Link]
M. Garni, T. Einfalt, M. Lomora, A. CarW. MeierC. G. PalivanArtificial Organelles: Reactions inside Protein–Polymer Supramolecular Assemblies“ Chimia 6, 424 (2016). [Link]
V. Mikhalevich, C. Zelmer, A. CarC. G. PalivanW. MeierBio-inspired Polymer Membranes“ Bio-inspired Polymers 22, 221-58 (2016). [Link]
I. A. Dinu, J. T. Duskey, A. CarC. G. PalivanW. MeierEngineered non-toxic cationic nanocarriers with photo-triggered slow-release properties“ Polym. Chem. 7, 3451 (2016). [Link]
A. Najer, S. Thamboo, C. G. Palivan, H. Beck, W. MeierGiant Host Red Blood Cell Membrane Mimicking Polymersomes Bind Parasite Proteins and Malaria Parasites“ Chimia 4, 288 (2016). [Link]
S. J. Sigg, V. Postupalenko, J. T. Duskey, C. G. PalivanW. MeierStimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles“ Biomacromolecules 17, 935-45 (2016). [Link]
X. Zhang, M. Lomora, T. Einfalt, W. Meier, N. Klein, D. Schneider, C. G. PalivanActive surfaces engineered by immobilizing protein-polymer nanoreactors for selectively detecting sugar alcohols“ Biomaterials 89, 79 (2016). [Link]
G. Gunkel-GraboleA. Car, V. V. Naik, L. Marot, G. Ferk, C. G. PalivanW. MeierPEG Brushes on Porous, PDMS-Coated Surfaces and Their Interaction with Carbon Dioxide“ Macromol. Chem. Phys. 217, 966 (2016). [Link]
C. G. Palivan, R. Goers, A. Najer, X. Zhang, A. CarW. MeierBioinspired polymer vesicles and membranes for biological and medical applications“ Chem. Soc. Rev. 45, 377 (2015). [Link]
A. Najer, S. Thamboo, J. T. Duskey, W. MeierC. G. PalivanAnalysis of Molecular Parameters Determining the Antimalarial Activity of Polymer-Based Nanomimics“ Macromol. Rapid Commun. 36, 1923 (2015). [Link]
J. Liu, V. Postupalenko, J. T. Duskey, C. G. PalivanW. MeierV. MikhalevichpH-Triggered Reversible Multiple Protein-Polymer Conjugation Based on Molecular Recognition“ J. Chem. Phys. B. 119, 12066 (2015). [Link]
G. Tsiavaliaris, F. Itel, K. Hedfalk, S. Al-Samir, W. Meier, G. Gros, V. Endeward “Low CO2 permeability of cholesterol-containing liposomes detected by stopped-flow fluorescence spectroscopy“ FASEB J. 29, 1780 (2015). [Link]
F. Itel, A. Najer, C. G. PalivanW. MeierDynamics of Membrane Proteins within Synthetic Polymer Membranes with Large Hydrophobic Mismatch“ Nano Lett. 15, 3871 (2015). [Link] [More Information] [Artikel in ChimieXtra]
J. Kowal, D. Wu, V. MikhalevichC. G. PalivanW. MeierHybrid Polymer–Lipid Films as Platforms for Directed Membrane Protein Insertion“ Langmuir 31, 4868 (2015). [Link]
T. Schuster, M. Nussbaumer, P. Baumann, N. Bruns, W. MeierA. CarPolymeric particulates for subunit vaccine delivery“ Subunit Vaccine Delivery, 181-201 (2015). [Link]
G. Gunkel-Grabole, S. Sigg, M. Lomora, S. Lörcher, C. G. PalivanW. MeierPolymeric 3D nano-architectures for transport and delivery of therapeutically relevant biomacromolecules“ Biomater. Sci. 2, 25 (2015). [Link]
A. Najer, D. Wu, A. Bieri, F. Brand, C. G. Palivan, H. P. Beck, W. MeierNanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites“ ACS Nano 8, 12560 (2014). [Link] [More Information]
F. Itel, M. Chami, A. Najer, S. Lörcher, D. Wu, I. A. Dinu, W. MeierMolecular organization and dynamics in polymersome membranes: A lateral diffusion study“ Macromolecules 47, 7588 (2014). [Link]
D. Wu, M. Spulber, F. Itel, M. Chami, T. Pfohl, C. G. PalivanW. MeierEffect of Molecular Parameters on the Architecture and Membrane Properties of 3D Assemblies of Amphiphilic Copolymers“ Macromolecules 47, 5060-69 (2014). [Link]

Who works with whom?

Prof. Wolfgang Meier from University of Basel (Department of Chemistry) leads this project and works with PhD student Viktoria Mikhalevich and with postdoc students Anja CarGesine Gunkel-Grabole and Jens Gaitzsch.

Group

Read more about the Meier-Group here.

Collaborations

The basis for molecular factories will be developed in collaboration with projects led by Daniel Müller, Dimitrios Fotiadis, Gebhard Schertler, Sven Panke, Viola Vogel, Thomas R. Ward, Janos Vörös and Thomas Pfohl.