39 research outputs found
Control of the stability and structure of liposomes by means of nanoparticles
Get PDFDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The interaction of bilayer vesicles with hard nanoparticles is of great relevance to the field of nanotechnology, e.g., its impact on health and safety matters, and also as vesicles are important as delivery vehicles. In this work we describe hybrid systems composed of zwitterionic phospholipid vesicles (DPPC), which are below the phase transition temperature, and added silica nanoparticles (SiNPs) of much smaller size. The initial DPPC unilamellar vesicles, obtained by extrusion, are rather unstable and age but the rate of ageing can be controlled over a large time range by the amount of added SiNPs. For low addition they become destabilized whereas larger amounts of SiNPs enhance the stability largely as confirmed by dynamic light scattering (DLS). ζ-Potential and DSC measurements confirm the binding of the SiNPs onto the phospholipid vesicles, which stabilizes the vesicles against flocculation by rendering the ζ-potential more negative. This effect appears above a specific SiNP concentration, and is the result of the adsorption of the negatively charged nanoparticles onto the outer surface of the liposome leading to decorated vesicles as proven by cryogenic transmission electron microscopy (cryo-TEM). Small amounts of surface-adsorbed SiNPs initially lead to a bridging of vesicles thereby enhancing flocculation, while higher amounts render the vesicles much more negatively charged and thereby long-time stable. This stability has an optimum at neutral pH and for low ionic strength. Thus we show that the addition of the SiNPs is a versatile way to control the stability of gel-state phospholipid vesicles and also to modulate their surface structure in a systematic fashion. This is not only of importance for understanding the fundamental interaction between SiNPs and bilayer vesicles, but also with respect to using silica particles as formulation aids for phospholipid dispersions.DFG, GRK 1524, Self-Assembled Soft-Matter Nanostructures at Interface
The Partnership Co-Design Lab: Co-constructing a Patient Advisor Programme to increase adherence to rehabilitation after upper extremity replantation
Get PDFA five-phase Patient Advisor Programme created by the Partnership Co-Design Lab led to higher rates of adherence to rehabilitation interventions for patients followed at the main rehabilitation centre compared to patients transferred to other, more remote, rehabilitation facilities
A Feedback Quenched Oscillator Produces Turing Patterning with One Diffuser
Get PDFEfforts to engineer synthetic gene networks that spontaneously produce patterning in multicellular ensembles have focused on Turing's original model and the “activator-inhibitor” models of Meinhardt and Gierer. Systems based on this model are notoriously difficult to engineer. We present the first demonstration that Turing pattern formation can arise in a new family of oscillator-driven gene network topologies, specifically when a second feedback loop is introduced which quenches oscillations and incorporates a diffusible molecule. We provide an analysis of the system that predicts the range of kinetic parameters over which patterning should emerge and demonstrate the system's viability using stochastic simulations of a field of cells using realistic parameters. The primary goal of this paper is to provide a circuit architecture which can be implemented with relative ease by practitioners and which could serve as a model system for pattern generation in synthetic multicellular systems. Given the wide range of oscillatory circuits in natural systems, our system supports the tantalizing possibility that Turing pattern formation in natural multicellular systems can arise from oscillator-driven mechanisms
The Dual Targeting of FcRn and FcγRs via Monomeric Fc Fragments Results in Strong Inhibition of IgG-Dependent Autoimmune Pathologies
Get PDFNovel molecules that directly target the neonatal Fc receptor (FcRn) and/or Fc gamma receptors (FcγRs) are emerging as promising treatments for immunoglobulin G (IgG)-dependent autoimmune pathologies. Mutated Fc regions and monoclonal antibodies that target FcRn are currently in clinical development and hold promise for reducing the levels of circulating IgG. Additionally, engineered structures containing multimeric Fc regions allow the dual targeting of FcRn and FcγRs; however, their tolerance needs to first be validated in phase I clinical studies. Here, for the first time, we have developed a modified monomeric recombinant Fc optimized for binding to all FcRns and FcγRs without the drawback of possible tolerance associated with FcγR cross-linking. A rational approach using Fc engineering allowed the selection of LFBD192, an Fc with a combination of six mutations that exhibits improved binding to human FcRn and FcγR as well as mouse FcRn and FcγRIV. The potency of LFBD192 was compared with that of intravenous immunoglobulin (IVIg), an FcRn blocker (Fc-MST-HN), and a trimeric Fc that blocks FcRn and/or immune complex-mediated cell activation through FcγR without triggering an immune reaction in several in vitro tests and validated in three mouse models of autoimmune disease
