Dynamics of Membrane Proteins within Synthetic Polymer Membranes with Large Hydrophobic Mismatch

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Malaria is an infectious disease that needs to be addressed using innovative approaches to counteract spread of drug resistance and to establish or optimize vaccination strategies. With our approach, we aim for a dual action with drug-and 'vaccine-like' activity against malaria. By inhibiting entry of malaria parasites into host red blood cells (RBCs) -using polymer vesicle-based (polymersome) nanomimics of RBC membranes -the life cycle of the parasite is interrupted and the exposed parasites are accessible to the host immune system. Here, we describe how host cell-sized RBC membrane mimics, formed with the same block copolymers as nanomimics, also bind the corresponding malaria parasite ligand and whole malaria parasites, similar to nanomimics. This was demonstrated using fluorescence imaging techniques and confirms the suitability of giant polymersomes (GUVs) as simple mimics for RBC membranes.

Section: Giant Host Red Blood Cell Membrane Mimicking Polymersomes Bimentioning

confidence: 99%

Giant Host Red Blood Cell Membrane Mimicking Polymersomes Bind Parasite Proteins and Malaria Parasites

Najer¹,

Thamboo²,

Palivan³

et al. 2016

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“…[22] We transferred PDMS-b-PMOXA copolymers with different lengths and hydrophobic to hydrophilic ratio and two different lipids on solid support, and investigated the distribution of the potassium channel MloK1 functional insertion of the biomolecules as proved for various biopores and membrane proteins. [16,17] We extended the insertion of membrane proteins in planar solid-supported membranes in collaboration with the group of C. Palivan (University of Basel). The first example of a successful insertion of a biopore in a completely artificial tethered, solid-supported membrane (TSSBM) of amphiphilic poly(butadiene)-blockpoly(ethylene oxide) (PB-PEO) copolymers has been obtained for the model bacterial membrane polypeptide α-haemolysin, αHL (Fig.…”

Section: Functional Synthetic Membranes By Insertion Of Biomolecules mentioning

confidence: 99%

“…Both diblock and triblock copolymers, such as poly(dimethylsiloxane)-block-poly(2-methyloxazoline) (PDMS-PMOXA) and (PMOXA-PDMS-PMOXA), known to be biocompatible have been synthesized with appropriate hydrophobic-to-hydrophilic ratio and formed compartments with membranes with the necessary fluidity [15] to allow insertion of membrane proteins. [16] Interestingly, the high hydrophilic mismatch between the size of the membrane proteins and the thickness of the synthetic membrane has been overcome by the membrane flexibility, which allowed a boundaries, consist of lipid bilayers with a variety of incorporated biomolecules, such as membrane proteins. [9] Membrane proteins play a central role in basically all physiological processes, and therefore constitute about 60% of approved drug targets.…”

Section: Introductionmentioning

confidence: 99%

'Active Surfaces' as Possible Functional Systems in Detection and Chemical (Bio) Reactivity

Housecroft

Palivan

Gademann

et al. 2016

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This article presents design strategies to demonstrate approaches to generate functionalized surfaces which have the potential for application in molecular systems; sensing and chemical reactivity applications are exemplified. Some applications are proven, while others are still under active investigation. Adaptation and extension of our strategies will lead to interfacing of different type of surfaces, specific interactions at a molecular level, and possible exchange of signals/cargoes between them. Optimization of the present approaches from each of five research groups within the NCCR will be directed towards expanding the types of functional surfaces and the properties that they exhibit.

“…The explanation for this interesting behavior for the membrane proteins in synthetic thick membranes is the high flexibility of the PDMS domain, which induces membrane fluidity similar to phospholipid bilayers. [15] Reconstitution of membrane proteins/biopores to allow transport of ions/ molecules is essential for reactions to be performed in confined nanospaces, such as nanoreactors and artificial organelles. In this respect, we were able to insert in a functional manner both biopores and membrane proteins in synthetic flexible membranes based on PMOXA-PDMS and PMOXA-PDMS-PMOXA amphiphilic copolymers.…”

Section: Introductionmentioning

confidence: 99%

Artificial Organelles: Reactions inside Protein–Polymer Supramolecular Assemblies

Garni

Einfalt

Lomora

et al. 2016

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Reactions inside confined compartments at the nanoscale represent an essential step in the development of complex multifunctional systems to serve as molecular factories. In this respect, the biomimetic approach of combining biomolecules (proteins, enzymes, mimics) with synthetic membranes is an elegant way to create functional nanoreactors, or even simple artificial organelles, that function inside cells after uptake. Functionality is provided by the specificity of the biomolecule(s), whilst the synthetic compartment provides mechanical stability and robustness. The availability of a large variety of biomolecules and synthetic membranes allows the properties and functionality of these reaction spaces to be tailored and adjusted for building complex self-organized systems as the basis for molecular factories.