About this episode
Cell membranes are critical for life. Effectively extracting proteins with naturally associated lipids from cell membranes is necessary for research, but traditional methods may damage these membrane components and limit the accuracy of scientific data. Dr Youzhong Guo at Virginia Commonwealth University has recently developed a revolutionary method for extracting membrane components in the form of Native Cell Membrane Nanoparticles. His team’s exciting work advances our understanding of the structure, function and interactions of membrane proteins and lipids. More
Cell membranes are an essential constituent of all living organisms. Cell membranes protect and organize cells and perform a range of vital functions that ensure an organism’s survival. Given the critical role of cell membranes, it is unsurprising that much research is dedicated to understanding their structure and function.
The two fundamental components of cell membranes are proteins and lipids, which form a diverse and complex system connecting the membrane to the wider cell. Interactions between cell-membrane proteins and between proteins and lipids play vital roles in myriad biological processes – including cell-to-cell communication, metabolic regulation and sensing environmental signals.
Understanding these interactions is, therefore, critical for identifying the mechanisms behind many medical disorders, in order to find ways of treating them. In-depth knowledge of these interactions is also crucial for designing targeted drug delivery systems and effective vaccines.
Scientists have traditionally used detergents to extract proteins from cell membranes to study them. However, detergents can cause structural damage to protein and lipid molecules, thus altering their functionality and hindering meaningful research.
Recently, Dr Youzhong Guo and his team at Virginia Commonwealth University’s Department of Medicinal Chemistry have revolutionized the extraction of cell membrane components using detergent-free processes. To do so, they have developed a technique to produce ‘native cell-membrane nanoparticles’ from cell membranes.
In this technique, the team uses polymers that form nanoparticles when they come in contact with cell membranes. As these nanoparticles form, membrane proteins and lipids become encapsulated within them. The nanoparticles protect these molecules so that they can be isolated and analysed.
In one study exploring the utility of their native cell-membrane nanoparticle system, Dr Guo and his colleagues extracted proteins that act as a transporter to expel molecules from within the cell. The researchers successfully extracted these membrane proteins without damaging them using their Native Cell Membrane Nanoparticles system.
By incubating the membrane proteins in the form of Native Cell Membrane Nanoparticles with liposomes, they were then able to create structures called ‘proteoliposomes’. Proteoiposomes mimic the cell-membrane environment, allowing scientists to study how proteins would behave in a real cell membrane.
Through further experiments, Dr Guo and his team demonstrated that the proteoliposomes could be used for studying the behaviour of protein channels within cell membranes. They also demonstrated that these proteoliposomes could be used to carry drugs and release them when they come in contact with acidic tissue, such as inflamed or cancerous cells.
Recently, Dr Guo thoroughly evaluated the available methods for extracting membrane components. He compared the ability of each technique to preserve the structure of protein and lipid molecules.
Interestingly, he found that the most commonly used detergent-free extraction methods did not perform any better than detergent-based methods. In contrast, the Native Cell Membrane Nanoparticle system his team developed demonstrated superior preservation of lipids and proteins, producing samples of sufficient quality to perform high-resolution structural analysis.
In their Native Cell Membrane Nanoparticles system, Dr Guo and his team use a number of different polymers that can form nanoparticles and encapsulate membrane components for analysis. Indeed, the significant differences in cell membranes between animals, plants, fungi and bacteria mean that it is likely impossible to obtain a single polymer that would protect the structures of all membrane proteins and lipids.
In fact, each type of membrane protein may need a specific set of polymers to aid their extraction. Toward this aim, Dr Guo and his team are building an extensive library of ‘membrane-active’ polymers. This library will enable researchers across the globe to choose the most appropriate polymer for the protein or cell type that they wish to study.
The research carried out by Dr Guo’s team is revolutionizing our understanding of cell membranes, and there is plenty more to come. This exciting area of biological research holds much promise for advancing the study of cell membrane components and their many fascinating interactions. Through a deeper understanding of the structure and function of membrane components, scientists will be empowered to develop effective therapies for a diverse range of medical conditions.
Original Article Reference
This Audio is a summary of the papers: ‘Detergent-free systems for structural studies of membrane proteins’, in Biochemical Society Transactions, doi.org/10.1042/BST20201080; ‘A native cell membrane nanoparticles system allows for high-quality functional proteoliposome reconstitution’, in BBA Advances, doi.org/10.1016/j.bbadva.2021.100011; and ‘Native Cell Membrane Nanoparticles System for Membrane Protein-Protein Interaction Analysis’, in Journal of Visualized Experiments, doi.org/10.3791/61298.
For further information, you can connect with Dr Youzhong Guo at email@example.com
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