The ART of ARTificial Membrane Systems
Analysing proteins in artificial environments, particularly using liposome systems to reconstitute isolated proteins and create "artificial cells" offers a range of benefits that significantly contribute to our understanding of biological processes.
Liposome-based artificial cells provide a controlled and reproducible platform that mimics the essential features of natural cellular environments. This allows studying proteins in a context that closely resembles the complexity of living cells, facilitating more realistic observations and interpretations.
Even though these “artificial cells” provide advantages compared to their biological inspiration, preparing these systems provides some challenges. In our research, we focus on developing a better understanding of the established surfactant-mediated approach of protein reconstitution as well as diving into microfluidics. Later one offers several advantages including:
- Precise Control of Size and Composition
- High Throughput and Scalability
- Reduced Batch-to-Batch Variability
- Minimization of Surfactant Residues
- Gradient Generation for Encapsulation Efficiency
- Diverse Liposome Morphologies
- Real-Time Monitoring and Analysis
- Integration with Downstream Processes
Improving the reconstitution process (concerning quality and quantity) has the potential to be beneficial for a variety of proteins, reaching from Ion Channels and Transporters to Receptors, Enzymes, Photosynthetic Proteins and more.
Lipid membranes under oxidative stress
The dynamic process of lipid peroxidation holds profound implications for cellular health and function, focusing on fundamental changes in the main building blocks of our cells.
At its core, lipid peroxidation is a chain reaction initiated by the presence of reactive oxygen species (ROS) or free radicals within the cellular environment. These highly reactive entities, often byproducts of normal cellular processes or external stressors, set off a cascade of events that lead to the oxidative degradation of lipids.
Lipid peroxidation has far-reaching consequences for cellular health. The compromised integrity of cell membranes can lead to increased permeability, altered fluidity, and disruptions in essential cellular processes. Furthermore, the byproducts of lipid peroxidation can act as signalling molecules, influencing cellular pathways related to inflammation, apoptosis, and oxidative stress response.
Our artificial membrane systems replicate the lipid composition found in the inner and outer mitochondria membrane. Mitochondria are primary sites for the generation of ROS, natural byproducts of the electron transport chain during cellular respiration. The high electron density in this process makes mitochondrial membranes particularly vulnerable to oxidative stress, initiating lipid peroxidation. Lipid peroxidation in mitochondrial membranes can disrupt the efficiency of the electron transport chain and compromise oxidative phosphorylation, ultimately affecting the production of adenosine triphosphate (ATP). This disruption in energy production has implications for cellular bioenergetics and overall cell function.
Lipids in Drug Delivery Systems
Liposome-based biocatalyst systems have gained prominence due to their ability to encapsulate enzymes within the liposomal lumen, providing a protected and controlled environment for catalysis (see below):
The encapsulation of enzymes within liposomes offers advantages such as protection from environmental factors, controlled release of substrates and products, and improved stability, making them valuable tools for a range of applications in biotechnology and beyond. While a variety of techniques are available for the encapsulation of proteins, one main problem of pure liposome systems lies in the rather low stability of the used phospholipids. To improve their stability, moving to hybrid nanospheres by incorporating inorganic materials. Especially coating the vesicles helps enhance the stability, functionality, and overall performance of liposome-based biocatalysts. In our group, we aim to (i) analyse the driving interaction patterns to form hybrid nanospheres and (ii) study the reason for the improved catalytic activity for encapsulated species.
