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

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.

Publications

E. V. Konishcheva, D. Daubian, S. Rigo, W. Meier “Probing membrane asymmetry of ABC polymersomes“ Chem. Commun. 2019. [DOI]
A. Angelini, C. Fodor, W. Yave, L. Leva, A. Car, W. Meier “pH-Triggered Membrane in Pervaporation Process“ ACS Omega 2018. [DOI]
M. Garni, R. Wehr, S. Yorulmaz Avsar, C. John, C. G. PalivanW. Meier “Polymer membranes as templates for bio-applications ranging from artificial cells to active surfaces“ Eur. Polym. J. 2018. [DOI]
E. V. Konishcheva, U. E. Zhumaev, W. Meier “Self-Assembly of PEO-b-PCL-b-PMOXA Binary Mixtures“ Macromolecules 2018. [DOI]
S. Rigo, G. Gunkel-Grabole, W. MeierC. G. Palivan “Surfaces with Dual Functionality through Specific Coimmobilization of Self-Assembled Polymeric Nanostructures“ 2018. [DOI]
M. E. Idrissi, C. E. Meyer, L. Zartner, W. Meier “Nanosensors based on polymer vesicles and planar membranes: a short review“ J. Nanobiotechnol. 2018. [DOI]
M. Garni, T. Einfalt, R. Goers, C. G. PalivanW. Meier “Live follow-up of enzymatic reactions inside the cavities of synthetic giant unilamellar vesicles (GUVs) equipped with membrane proteins mimicking cell architecture“ ACS Synth. Biol. 2018. [DOI]
C. L. Draghici, V. Mikhalevich, G. Gunkel-Grabole, J. Kowal, W. MeierC. G. Palivan “Biomimetic planar Polymer Membranes decorated with Enzymes as Functional Surfaces“ Langmuir 2018. [DOI]
R. Goers, J. Thoma, N. Ritzmann, A. Di Silvestro, C. Alter, G. Gunkel-Grabole, D. FotiadisD. J. MüllerW. Meier “Optimized reconstitution of membrane proteins into synthetic membranes“ Commun. Chem. 2018. [DOI]
A. Najer, C. G. Palivan, H. Beck, W. Meier “Challenges in Malaria Management and a Glimpse at Some Nanotechnological Approaches“ Infectious Diseases and Nanomedicine III 2018. [DOI]
M. Vandenbossche, G. Gunkel-Grabole, A. Car, L. Bernard, P. Rupper, K. Maniura-Weber, M. Heuberger, G. Faccio, D. Hegemann “Near-Surface Structure of Plasma Polymer Films Affects Surface Behavior in Water and its Interaction with Proteins“ Plasma Chem. Plasma Process. 2018. [DOI]
J. Gaitzsch, P. C. Welsch, J. Folini, C. Schoenenberger, J. C. Anderson, W. Meier “Revisiting Monomer Synthesis and Radical Ring Opening Polymerization of Dimethylated MDO Towards Biodegradable Nanoparticles for Enzymes“ Eur. Polym. J. 2018. [DOI]
E. Konishcheva, D. Daubian, J. GaitzschW. Meier “Synthesis of Linear ABC Triblock Copolymers and Their Self-Assembly in Solution“ Helv. Chim. Acta 2018. [DOI]
A. Lanzilotto, M. Kyropoulou, E. C. Constable, C. E. HousecroftW. MeierC. G. Palivan “Porphyrin-polymer nanocompartments: singlet oxygen generation and antimicrobial activity“ 2017. [DOI]
J. Gaitzsch, L. Messager, E. Morecroft, W. Meier “Vesicles in Multiple Shapes: Fine-Tuning Polymersomes’ Shape and Stability by Setting Membrane Hydrophobicity“ Polymers 2017, 9(10):483. [DOI]
E. V. Konishcheva, U. E. Zhumaev, M. Kratt, V. Oehri, W. Meier “Complex Self-Assembly Behavior of Bis-hydrophilic PEO-b-PCL-b-PMOXA Triblock Copolymers in Aqueous Solution“ Macromolecules 2017. [DOI]
C. Edlinger, T. Einfalt, M. Spulber, A. Car, W. MeierC. G. Palivan “Biomimetic Strategy To Reversibly Trigger Functionality of Catalytic Nanocompartments by the Insertion of pH-Responsive Biovalves“ Nano Lett. 2017. [DOI]
V. Mikhalevich, I. Craciun, M. Kyropoulou, C. G. PalivanW. Meier “Amphiphilic peptide self-assembly: Expansion to hybrid materials“ Biomacromolecules 2017. [DOI]
G. Gunkel-Grabole, C. G. PalivanW. Meier “Nanostructured Surfaces through Immobilization of Self-Assembled Polymer Architectures Using Thiol–Ene Chemistry“ Macromol. Mater. Eng. 2017, 302:1600363. [DOI]
I. Craciun, G. Gunkel-Grabole, A. Belluati, C. G. PalivanW. Meier “Expanding the potential of MRI contrast agents through multifunctional polymeric nanocarriers“ Nanomedicine 2017, 12:811-17. [DOI]
S. MatileW. MeierC. G. Palivan “Strain-Promoted Thiol-Mediated Cellular Uptake of Giant Substrates: Liposomes and Polymersomes“ Angew. Chem. Int. Ed. 2017, 56:2947-50. [DOI]
S. Lörcher, W. Meier “Cosolvent fractionation of PMOXA-b-PDMS-b-PMOXA: Bulk separation of triblocks from multiblocks“ Eur. Polym. J. 2017. [DOI]
E. V. Konishcheva, U. E. Zhumaev, W. Meier “PEO-b-PCL-b-PMOXA Triblock Copolymers: From Synthesis to Microscale Polymersomes with Asymmetric Membrane“ Macromolecules 2017. [DOI]
P. Baumann, M. Spulber, O. Fischer, A. Car, W. Meier “Investigation of Horseradish Peroxidase Kinetics in an “Organelle-Like” Environment“ Small 2017, 13:1603943. [DOI] [More Information]
J. Liu, V. Postupalenko, S. Lörcher, D. Wu, M. Chami, W. MeierC. G. Palivan “DNA-Mediated Self-Organization of Polymeric Nanocompartments Leads to Interconnected Artificial Organelles“ Nano Lett. 2016:DOI: 10.1021/acs.nanolett.6b03430. [DOI] [More Information]
D. Vasquez, T. Einfalt, W. MeierC. G. Palivan “Asymmetric Triblock Copolymer Nanocarriers for Controlled Localization and pH-Sensitive Release of Proteins“ Langmuir 2016, 32:10235-43. [DOI]
S. J. Sigg, F. Santini, A. Najer, P. U. Richard, W. MeierC. G. Palivan “Nanoparticle-based highly sensitive MRI contrast agents with enhanced relaxivity in reductive milieu“ Chem. Commun. 2016, 52:9937-40. [DOI]
D. Harder, S. Hirschi, Z. Ucurum, R. Goers, W. MeierD. J. MüllerD. Fotiadis “Engineering a Chemical Switch into the Light-driven Proton Pump Proteorhodopsin by Cysteine Mutagenesis and Thiol Modification“ Angew. Chem. Int. Ed.  2016, 55:8846. [DOI]
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. Meier “An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery“ Nanoscale 2016:DOI: 10.1039/C6NR04290B. [DOI]
S. HirschiM. Stauffer, D. Harder, D. J. MüllerW. MeierD. Fotiadis “Engineering and Assembly of Protein Modules into Functional Molecular Systems“ Chimia 2016, 6:398. [DOI]
Y. Cotelle, N. Chuard, S. Lascano, V. Lebrun, R. Wehlauch, N. Bohni, S. Lörcher, V. Postupalenko, S. ReddyW. MeierC. G. Palivan, K. Gademann, T. R. WardS. Matile “Interfacing Functional Systems“ Chimia 2016, 6:418. [DOI]
C. E. HousecroftC. G. Palivan, K. Gademann, W. Meier, M. Calame, V. Mikhalevich, X. Zhang, E. Piel, M. Szponarski, A. Wiesler, A. Lanzilotto, E. C. Constable, A. Fanget, R. Stoop “‘Active surfaces’ as Possible Functional Systems in Detection and Chemical (Bio) Reactivity“ Chimia 2016, 6:402. [DOI]
M. Garni, T. Einfalt, M. Lomora, A. Car, W. MeierC. G. Palivan “Artificial Organelles: Reactions inside Protein–Polymer Supramolecular Assemblies“ Chimia 2016, 6:424. [DOI]
V. Mikhalevich, C. Zelmer, A. Car, C. G. PalivanW. Meier “Bio-inspired Polymer Membranes“ Bio-inspired Polymers 2016, 22:221-58. [DOI]
I. A. Dinu, J. T. Duskey, A. Car, C. G. PalivanW. Meier “Engineered non-toxic cationic nanocarriers with photo-triggered slow-release properties“ Polym. Chem. 2016, 7:3451. [DOI]
A. Najer, S. Thamboo, C. G. Palivan, H. Beck, W. Meier “Giant Host Red Blood Cell Membrane Mimicking Polymersomes Bind Parasite Proteins and Malaria Parasites“ Chimia 2016, 4:288. [DOI]
S. J. Sigg, V. Postupalenko, J. T. Duskey, C. G. PalivanW. Meier “Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles“ Biomacromolecules 2016, 17:935-45. [DOI]
X. Zhang, M. Lomora, T. Einfalt, W. Meier, N. Klein, D. Schneider, C. G. Palivan “Active surfaces engineered by immobilizing protein-polymer nanoreactors for selectively detecting sugar alcohols“ Biomaterials 2016, 89:79. [DOI]
G. Gunkel-Grabole, A. Car, V. V. Naik, L. Marot, G. Ferk, C. G. PalivanW. Meier “PEG Brushes on Porous, PDMS-Coated Surfaces and Their Interaction with Carbon Dioxide“ Macromol. Chem. Phys. 2016, 217:966. [DOI]
C. G. Palivan, R. Goers, A. Najer, X. Zhang, A. Car, W. Meier “Bioinspired polymer vesicles and membranes for biological and medical applications“ Chem. Soc. Rev. 2015, 45:377. [DOI]
A. Najer, S. Thamboo, J. T. Duskey, W. MeierC. G. Palivan “Analysis of Molecular Parameters Determining the Antimalarial Activity of Polymer-Based Nanomimics“ Macromol. Rapid Commun. 2015, 36:1923. [DOI]
J. Liu, V. Postupalenko, J. T. Duskey, C. G. PalivanW. MeierV. Mikhalevich “pH-Triggered Reversible Multiple Protein-Polymer Conjugation Based on Molecular Recognition“ J. Chem. Phys. B. 2015, 119:12066. [DOI]
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. 2015, 29:1780. [DOI]
F. Itel, A. Najer, C. G. PalivanW. Meier “Dynamics of Membrane Proteins within Synthetic Polymer Membranes with Large Hydrophobic Mismatch“ Nano Lett. 2015, 15:3871. [DOI] [More Information] [Artikel in ChimieXtra]
J. Kowal, D. Wu, V. MikhalevichC. G. PalivanW. Meier “Hybrid Polymer–Lipid Films as Platforms for Directed Membrane Protein Insertion“ Langmuir 2015, 31:4868. [DOI]
T. Schuster, M. Nussbaumer, P. Baumann, N. Bruns, W. Meier, A. Car “Polymeric particulates for subunit vaccine delivery“ Subunit Vaccine Delivery 2015:181-201. [DOI]
G. Gunkel-Grabole, S. Sigg, M. Lomora, S. Lörcher, C. G. PalivanW. Meier “Polymeric 3D nano-architectures for transport and delivery of therapeutically relevant biomacromolecules“ Biomater. Sci. 2015, 2:25. [DOI]
A. Najer, D. Wu, A. Bieri, F. Brand, C. G. Palivan, H. P. Beck, W. Meier “Nanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites“ ACS Nano 2014, 8:12560. [DOI] [More Information]
F. Itel, M. Chami, A. Najer, S. Lörcher, D. Wu, I. A. Dinu, W. Meier “Molecular organization and dynamics in polymersome membranes: A lateral diffusion study“ Macromolecules 2014, 47:7588. [DOI]
D. Wu, M. Spulber, F. Itel, M. Chami, T. Pfohl, C. G. PalivanW. Meier “Effect of Molecular Parameters on the Architecture and Membrane Properties of 3D Assemblies of Amphiphilic Copolymers“ Macromolecules 2014, 47:5060-69. [DOI]