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BIOINSPIRED FUNCTIONAL PROTEIN-POLYMER SUPRAMOLECULAR NANOASSEMBLIES

English title BIOINSPIRED FUNCTIONAL PROTEIN-POLYMER SUPRAMOLECULAR NANOASSEMBLIES
Applicant Palivan Cornelia
Number 172604
Funding scheme Project funding
Research institution Physikalische Chemie Departement Chemie Universität Basel
Institution of higher education University of Basel - BS
Main discipline Physical Chemistry
Start/End 01.07.2017 - 30.06.2021
Approved amount 253'054.00
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Keywords (5)

Nano-compartiments polymériques; organelles artificielles; réactions en cascade; enzymes; protéines membranaires

Lay Summary (French)

Lead
La nanotechnologie propose de plus en plus de solutions innovantes pour répondre à des besoins dans le domaine des traitements médicaux, de production de substances ou pour détecter d’une manière précise et rapide la présence des molécules d’intérêt. Une des stratégies les plus prometteuses est de combiner des biomolécules (enzymes, protéines, ADN) avec des ensembles synthétiques nanométriques à base de polymères (micelles, vésicules, nanoparticules, nanotubes) pour pouvoir générer des matériaux hybrides qui miment les structures et les fonctions naturelles. Ces matériaux bio-hybrides ont pour avantages l’activité et la spécificité des biomolécules ainsi que la stabilité et la topologie précise des ensembles synthétiques. Ceci leur permet de surpasser les ensembles conventionnels en termes d’efficacité et fonctionnalité.
Lay summary

Contenu et objectives du travail de recherche
Le projet, inspiré par les organelles naturelles qui sont des éléments essentiels des cellules, a comme but de développer des « nano-compartiments catalytiques » à l’intérieur desquels des réactions spécifiques auront lieu, pour produire des substances d’intérêt dans les meilleures conditions de contrôle et d’efficacité. Ces nano-compartiments catalytiques sont générés par encapsulation des biomolécules (enzymes, protéines) dans des compartiments nanométriques et insertion des protéines membranaires dans leurs parois. Les protéines membranaires serviront de « portes » nanométriques pour les molécules des réactions : les substrats nécessaires pour l’activité des enzymes/protéines et les produits des réactions qui vont être libérés par les nano-compartiments. De plus, le projet va développer des réactions en cascade entre différents nano-compartiments catalytiques par encapsulation de protéines différentes dans des compartiments situés à proximité. Nos nano-compartiments catalytiques à base de biomolécules serviront de simples « organelles artificielles » et vont soutenir des réactions en cascade qui simulent la communication ayant lieu entre les organelles naturelles dans les cellules.  Ces nano-compartiments catalytiques « en tandem » vont offrir de nouvelles solutions dans plusieurs domaines dont la nano-médecine, la technologie, ou la chimie.

Contexte scientifique et social du projet de recherche
L’objectif de ces recherches sera d’étudier des réactions enzymatiques en cascade dans des compartiments nanométriques afin de comprendre leurs conditions et de les améliorer pour produire et libérer de manière contrôlée les molécules désirées, comme par exemple des médicaments, biomolécules or molécules fluorescentes. De plus, ces nano-compartiments catalytiques qui combinent des biomolécules avec des ensembles synthétiques serviront comme simples modèles des organelles naturelles dans les cellules.

Direct link to Lay Summary Last update: 07.08.2019

Responsible applicant and co-applicants

Employees

Project partner

Publications

Collaboration

Group / person Country
Types of collaboration
Prof. Wolfgang Meier, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Richard Kamerer, PSI Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Biointerfaces International Conference Poster Development of self-assembling peptide particles for gene delivery applications 18.08.2021 on line conference, Switzerland Palivan Cornelia; Skowicki Michal Jerzy;
NICE International Conference Talk given at a conference Transfer of nanoscale objects into GPMVs as cellular model systems 12.10.2020 Nice, France Zartner Luisa; Palivan Cornelia;
NICE International Conference Talk given at a conference Smart molecular factories based on bio-synthetic compartments as mimics of cells 12.10.2020 Nice, France Zartner Luisa; Palivan Cornelia;
Swiss Chemical Society Meeting Poster Transfer of Nanoscale Objects into Giant Plasma Membrane Vesicles (GPMVs) serving as cellular model systems 25.08.2020 on line conference, Switzerland Palivan Cornelia; Zartner Luisa;
Italian National Conference on the Physics of Matter Talk given at a conference How to mimic natural organelles by engineering bio-synthetic nanocompartments with in vivo functionality 30.09.2019 Catania, Italy Palivan Cornelia;
German Conference in Synthetic Biology Talk given at a conference Mimics of natural organelles based on bio-synthetic nanocompartments with in vivo functionality 11.09.2019 Aachen, Germany Palivan Cornelia;
7th International Symposium on Surfaces and Interfaces for Biomaterials Talk given at a conference Bioinspired molecular factories with architecture and in vivo functionality as mimics of natural organelles 22.07.2019 Quebec, Canada Palivan Cornelia;
83rd Prague Meeting on Macromolecules, Polymers in Medicine 2019 Talk given at a conference Bio-synthetic nanocompartments with in vivo functionality as artificial organelles 23.06.2019 Prague, Czech Republic Palivan Cornelia;
Nanyang Technological University Individual talk Bioinspired Molecular Factories with Architecture and in vivo Functionality as Artificial Organelles 27.11.2018 Singapore, Singapore Palivan Cornelia;
NICE International Conference Talk given at a conference Bioinspired Molecular Factories with Architecture and in vivo Functionality as Cell Mimics 14.10.2018 Nice, France Zartner Luisa; Palivan Cornelia;
ACS Meeting Talk given at a conference Biomimetic artificial organelles with in vitro and in vivo reduction triggered activity 20.08.2017 Washington, United States of America Palivan Cornelia;
TechMem 2017 Talk given at a conference Functional membranes based on protein-polymer membranes 07.08.2017 Wien, Austria Palivan Cornelia;


Associated projects

Number Title Start Funding scheme
163996 Interactions, Dynamics, and Functionality at Nanoscale Characterised by Confocal Laser Scanning Microscopy and Fluorescence Correlation Spectroscopy 01.12.2015 R'EQUIP
139133 Structure, dynamics and interactions of paramagnetic centers characterised by Electrn Paramagnetic Resonance 01.12.2011 R'EQUIP
207383 BIOINSPIRED MULTIFUNCTIONAL BIO-SYNTHETIC SUPRAMOLECULAR ASSEMBLIES 01.07.2022 Project funding
165859 DESIGN OF NANOREACTORS AND ARTIFICIAL ORGANELLES BASED ON POLYMER SUPRAMOLECULAR ASSEMBLIES 01.05.2016 Project funding

Abstract

The development of new functional materials by bottom-up approaches that combine different building blocks at the nanoscale in a novel architecture with improved or new properties and functionality is currently in focus for applications in various domains. One of the most promising strategies is to interface biomolecules (enzymes, proteins, DNA, biomimics) with synthetic assemblies that have a variety of architectures (micelles, vesicles, tubes, particles) in order to mimic natural structures and functions. Such bio-hybrid materials have the advantages of combining the activity and specificity of biomolecules with the stability and precise topology of a synthetic matrix, and thus underscore conventional systems in terms of efficacy and functionality. This project aims to develop functional protein-polymer assemblies, which will serve as new types of catalytic nanocompartments providing efficient and controlled reaction space for biomolecules by combining physical chemistry, nanoscience and enzyme biochemistry. In a biomimetic approach inspired by natural organelles in living cells, we will encapsulate/insert biomolecules (proteins, enzymes) in synthetic nanocompartments to create catalytic reaction spaces with different topology and functionality. We will produce catalytic nanocompartments with “triggered activity” so that in situ reactions inside compartments are activated by opening “protein gates” inserted inside the membrane. A complementary objective is based on producing catalytic nanocompartments acting “in tandem” to support cascade reactions involving a combination of different nanocompartments. Catalytic nanocompartments, producing desired molecules “on demand” serve as simple mimics of natural organelles, whereas those acting “in tandem” mimic chemical communication between organelles. The development of enzymatic reactions in the confined spaces of supramolecular assemblies with nanometer sizes represents a response to the increasing evidence of low bioavailability and stability of directly administrated biopharmaceuticals, and the necessity to produce/detect compounds by controlled cascade reactions between different spatial assemblies in new materials with complex functionality (electronics, medicine, catalysis, food science). The understanding at the molecular level of the relationships between the factors that support successful reactions in confined spaces with different topologies represents a major benefit of this project, which aims to combine model enzymatic reactions with complementary properties resulting from different architectures of the reaction spaces (single-, and in tandem- nanocompartments) Systematic variation of the nanocompartment properties (size, thickness of the membrane, concentration of compartments), and characteristics of the biomolecules (concentration, modification with specific molecular entities, ratio between different biomolecules) will produce efficient interfacing and result in new functional hybrid assemblies. The project combines a fundamental study of the structural changes and interactions that occur when a functional bio-hybrid assembly is generated with applied investigations of the relevant factors and conditions that characterise “model” enzymatic reactions for extension to other reactions necessary for translational applications. This will support the development of a rational design for an efficient platform of catalytic nanocompartments by optimizing the structural and functional details for each type of reaction space (single-, and in tandem- nanocompartments), and straightforward changes of biomolecule or the overall polymer assembly.
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