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Design, synthesis and characterization of lipidic nanomaterials for biomedical and biosensing applications

English title Design, synthesis and characterization of lipidic nanomaterials for biomedical and biosensing applications
Applicant Landau Ehud M.
Number 154451
Funding scheme Sinergia
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Physical Chemistry
Start/End 01.01.2015 - 31.12.2018
Approved amount 1'372'689.00
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All Disciplines (5)

Discipline
Physical Chemistry
Condensed Matter Physics
Organic Chemistry
Material Sciences
Biophysics

Keywords (8)

bioelectrochemistry; LCP crystallization; molecular transport; membrane proteins; lipid mesophases; lyotropic liquid crystals; lipid synthesis; small angle X-ray scattering

Lay Summary (German)

Lead
Membrane kommen in allen lebenden Organismen vor. Wissen und Verständnis der Struktur, Funktion und Dynamik von verschiedenen Membransystemen ist von wesentlicher Bedeutung in verschiedenen Wissenschaftsbereichen von der Biologie über Chemie zu den Materialwissenschaften. Verwendung der spezifischen strukturellen und dynamischen Materialeigenschaften von lipidischen kubischen Phasen (Lipidic Cubic Phases, LCPs) findet in verschiedenen Bereichen der Membranwissenschaften statt. Insbesondere die Kristallisation und Strukturaufklärung mit atomarer Auflösung von etwa 10% aller Membranproteine ist hervorzuheben. Trotz der zunehmenden Bedeutung von LCPs in den Membranwissenschaften sind die molekularen Mechanismen, welche der LCP-basierten Kristallisation zugrunde liegen, sowie die molekularen Wechselwirkungen zwischen Lipiden und Proteinen in solchen Mesophasen, noch unklar.
Lay summary

Das übergeordnete Ziel dieses Projekts ist der Entwurf, die Synthese und die Charakterisierung von neuartigen Lipiden, die zu funktionellen Lipidnanomaterialien geformt werden sowie die Anwendung solcher Materialien in einer Reihe wichtiger Probleme der Membranbiologie und Biophysik. Dazu gehören die Mechanismen der Membranprotein-Rekonstitution, -Orientierung und -Kristallisation innerhalb Lipid Mesophasen; grundlegende Aspekte über Transport und Dynamik in Mesophasen, die zu Anwendungen bei der Medikamentenverabreichung führen werden; sowie Herstellung von neuen auf Stimuli reagierenden mesoskopischen Matrizen. Fortschritte dieser Forschung, die an der Schnittstelle zwischen biophysikalischer Chemie, Physik und Technologie der weichen kondensierten Materie sowie Oberflächen- und Kolloidchemie liegt, werden unser Verständnis der komplexen strukturellen und dynamischen Wechselwirkungen zwischen Membranproteinen und Lipiden in mesoskopischen Biomaterialien verbessern und können in Biomedizin, Pharmazie und Lebensmitteltechnologie relevant sein.

Direct link to Lay Summary Last update: 18.12.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Design of ultra-swollen lipidic mesophases for the crystallization of membrane proteins with large extracellular domains
Zabara Alexandru, Chong Josephine Tse Yin, Martiel Isabelle, Stark Laura, Cromer Brett A., Speziale Chiara, Drummond Calum John, Mezzenga Raffaele (2018), Design of ultra-swollen lipidic mesophases for the crystallization of membrane proteins with large extracellular domains, in NATURE COMMUNICATIONS, 9, 544.
Lipidic Mesophases as Novel Nanoreactor Scaffolds for Organocatalysts: Heterogeneously Catalyzed Asymmetric Aldol Reactions in Confined Water
Duss Michael, Manni Livia Salvati, Moser Laurent, Handschin Stephan, Mezzenga Raffaele, Jessen Henning J., Landau Ehud M. (2018), Lipidic Mesophases as Novel Nanoreactor Scaffolds for Organocatalysts: Heterogeneously Catalyzed Asymmetric Aldol Reactions in Confined Water, in ACS APPLIED MATERIALS & INTERFACES, 10(5), 5114-5124.
Lipidic Cubic Phase-Induced Membrane Protein Crystallization: Interplay Between Lipid Molecular Structure, Mesophase Structure and Properties, and Crystallogenesis
Zabara Alexandru, Meikle Thomas G., Trenker Raphael, Yao Shenggen, Newman Janet, Peat Thomas S., Separovic Frances, Conn Charlotte E., Call Melissa J., Call Matthew E., Landau Ehud M., Drummond Calum J. (2017), Lipidic Cubic Phase-Induced Membrane Protein Crystallization: Interplay Between Lipid Molecular Structure, Mesophase Structure and Properties, and Crystallogenesis, in CRYSTAL GROWTH & DESIGN, 17(11), 5667-5674.
Charged additives modify drug release rates from lipidic cubic phase carriers by modulating electrostatic interactions
Nazaruk Ewa, Górecka Ewa, Osornio Yazmin M., Landau Ehud M., Bilewicz Renata (2017), Charged additives modify drug release rates from lipidic cubic phase carriers by modulating electrostatic interactions, in Journal of Electroanalytical Chemistry.
Active Gating, Molecular Pumping, and Turnover Determination in Biomimetic Lipidic Cubic Mesophases with Reconstituted Membrane Proteins
Speziale Chiara, Zabara Alexandru Florian, Drummond Calum John, Mezzenga Raffaele (2017), Active Gating, Molecular Pumping, and Turnover Determination in Biomimetic Lipidic Cubic Mesophases with Reconstituted Membrane Proteins, in ACS Nano, 11(11), 11687-11693.
Monoolein Cubic Phase Gels and Cubosomes Doped with Magnetic Nanoparticles–Hybrid Materials for Controlled Drug Release
Szlezak Monika, Nieciecka Dorota, Joniec Aleksandra, Pękała Marek, Gorecka Ewa, Emo Mélanie, Stébé Marie J., Krysiński Paweł, Bilewicz Renata (2017), Monoolein Cubic Phase Gels and Cubosomes Doped with Magnetic Nanoparticles–Hybrid Materials for Controlled Drug Release, in ACS Applied Materials & Interfaces, 9(3), 2796-2805.
A macroscopic H+ and Cl- ions pump via reconstitution of EcClC membrane proteins in lipidic cubic mesophases
Speziale Chiara (2016), A macroscopic H+ and Cl- ions pump via reconstitution of EcClC membrane proteins in lipidic cubic mesophases, in Proc. Natl. Acad. Sci. USA, 113, 7491.
Interactions of lipidic cubic phase nanoparticles with lipid membranes
Jablonowska Elżbieta (2016), Interactions of lipidic cubic phase nanoparticles with lipid membranes, in Langmuir, 32, 9640.
Biotinylated Cubosomes: A Versatile Tool for Active Targeting and Code livery of Paclitaxel and a Fluorescein-Based Lipid Dye
Aleandri Simone, Bandera Davide, Mezzenga Raffaele, Landau Ehud M. (2015), Biotinylated Cubosomes: A Versatile Tool for Active Targeting and Code livery of Paclitaxel and a Fluorescein-Based Lipid Dye, in LANGMUIR, 31(46), 12770-12776.
Lyotropic Cubic Phases for Drug Delivery: Diffusion and Sustained Release from the Mesophase Evaluated by Electrochemical Methods
Nazaruk Ewa, Miszta Przemyslaw, Filipek Slawomir, Gorecka Ewa, Landau Ehud M., Bilewicz Renata (2015), Lyotropic Cubic Phases for Drug Delivery: Diffusion and Sustained Release from the Mesophase Evaluated by Electrochemical Methods, in LANGMUIR, 31(46), 12753-12761.
PM-IRRAS studies of DMPC bilayers supported on Au(111) electrodes modified with hydrophilic monolayers of thioglucose.
Matyszewska Dorota, Bilewicz Renata, Su ZhangFei, Abbasi Fatemeh, Leitch J Jay, Lipkowski Jacek, PM-IRRAS studies of DMPC bilayers supported on Au(111) electrodes modified with hydrophilic monolayers of thioglucose., in Langmuir : the ACS journal of surfaces and colloids.

Collaboration

Group / person Country
Types of collaboration
Raimund Dutzler/University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Jan F. Biernat/University of Technology Gdansk Poland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Olivier Devuyst/University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Oliver Zerbe/University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Henning Jessen/University of Freiburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Nissim Garti/ Hebrew University of Jerusalem Israel (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Ben Boyd/Monash University Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Laurent Sagalowicz/ Nestlé Research Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
- Industry/business/other use-inspired collaboration
Jerzy Rogalski/University of Technology Gdansk Poland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Andreas Plückthun/University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Associated projects

Number Title Start Funding scheme
178997 Molecular Diffusion in Bicontinuous Cubic Phases 01.06.2018 Project funding (Div. I-III)

Abstract

Membranes are ubiquitous to all living systems, and progress in membrane biology, specifically membrane structural biology, has witnessed enormous advances in the past years. The classical fluid mosaic model of a membrane, in which hydrophobic integral components such as lipids and membrane proteins are constrained within the plane of the membrane, but are free to diffuse laterally, has been constantly refined, and knowledge and understanding of the structure, function and dynamics of various membrane subsystems is now available at atomic resolution. Whereas production of well-diffracting crystals of membrane protein was considered the most difficult hurdle in molecular membrane biology only two decades ago, conceptual and technological advances in recent years have resulted in a remarkable increase of available high resolution structures of membrane proteins and their complexes, with a concomitant deeper understanding of their function, dynamics and assembly. Among those advances, the concept of utilizing the distinct structural and dynamic material properties of lipidic cubic phases (LCPs) for the solubilization, stabilization and crystallization of membrane proteins, which was introduced by the UZH co-applicant of this proposal yielded about 10% of all membrane protein structures currently available, and all but one of the structures of the pharmacologically important G protein-coupled receptors (GPCRs). Intriguingly, this significant achievement was accomplished using but a few related monoacylglycerols whose chemical structure and function, as well as the ensuing phase behavior, are very similar. Moreover, despite the increased importance of LCPs in membrane studies, the molecular mechanisms underlying LCP-based crystallization, and the underlying molecular interactions between lipids and proteins in such mesophases, are still unclear.Progress in fundamental as well as applied aspects of membrane biology and biophysics thus calls for the design, synthesis and characterization of novel lipids and the judicious use of ensuing lipidic nanomaterials. Advances in this area, which lies at the interface between biophysical chemistry, soft condensed matter physics and technology, and surface and colloidal chemistry, will best be facilitated by an interdisciplinary approach. The current application brings together experts in the fields of lipid design and synthesis, membrane structural biology, soft condensed matter physics, drug delivery, electrochemistry, and surface chemistry, who are committed to address a number of inter-related issues. These include the mechanisms of membrane protein reconstitution, orientation and crystallization within lipidic mesophases; fundamental aspects of transport and dynamics in mesophases, which will lead to applications in drug delivery; and novel stimuli-responsive mesoscopic matrices.Elucidating these fundamental issues will enhance our understanding of the complex structural and dynamic interactions between membrane proteins and lipids within mesoscopic biomaterials, and may have relevance in biomedical science and technology, pharmaceutical science and even food technology.
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