Final Report Summary - COSMIC (Complex Synthetic Mimics of the Cell Membrane)
Our scientific vision was to create complex mimics of the cell membrane that will enable new insights into important biological phenomena and new biomimetic systems inspired by the biology of the cell membrane. During this project we have created a new range of tools that help us control and understand the complex phenomena present in cell membranes. These tools have enabled us to combine methods capable of resolving single molecules, and understand the role of crowding and diffusion in the complex environment of the cell.
This work has had impact in our understanding of biological processes relevant for antimicrobial resistance, signal transduction in the brain, and protein expression by bacteria. It has biotechnological implications for new methods for genome sequencing, and label-free imaging of cells.
Specifically, we have published a range of scientific papers focusing on a number of areas in which have helped highlight how artificial mimics of cells can improve our understanding of biological phenomena. This work programme was divided into a number of distinct areas:
We first focused on the role of crowding in the plasma membrane in modulating biological function. We have developed new methods to create artificial membrane systems with defined lipid mobility, where we can control the anomalous properties of diffusion in the membrane and use it to understand why such diffusion is anomalous in real cell membranes. We also developed new methods to dynamically control the composition in artificial membranes and exploited DNA origami nanotechnology to create a reconfigurable artificial cytoskeleton bound to lipid membranes. We also have gone beyond the original aims of the proposal to characterise a model cytoskeleton to work with collaborators (Gadgegaard, Glasgow) to fabricate nanostructure surfaces. This work is in preparation for publication, and will show the roles of topography and topology in controlling diffusive properties of cell membranes. Using these artificial lipid bilayers we have examined the folding mechanism of important proteins of bacterial outer membranes using optical methods with single-molecule resolution.
We have also developed methods to produce double bilayer structures, and work here has focused on characterising the steric effects on protein and peptide assembly in this artificial model of a cellular synapse. A manuscript is in preparation.
We have also completed work characterising methods of pore formation in membrane using single-molecule methods in our artificial bilayers. We have helped shed light on the fundamental principles governing electric field-induced pore formation, and important process used in food sterilisation, genetic modification, and tumour ablation. Similarly, we have studied the mechanism by which antimicrobial peptides induced pores, this work suggests a common mode of action across peptide classes previously thought to be dissimilar.
This work has had impact in our understanding of biological processes relevant for antimicrobial resistance, signal transduction in the brain, and protein expression by bacteria. It has biotechnological implications for new methods for genome sequencing, and label-free imaging of cells.
Specifically, we have published a range of scientific papers focusing on a number of areas in which have helped highlight how artificial mimics of cells can improve our understanding of biological phenomena. This work programme was divided into a number of distinct areas:
We first focused on the role of crowding in the plasma membrane in modulating biological function. We have developed new methods to create artificial membrane systems with defined lipid mobility, where we can control the anomalous properties of diffusion in the membrane and use it to understand why such diffusion is anomalous in real cell membranes. We also developed new methods to dynamically control the composition in artificial membranes and exploited DNA origami nanotechnology to create a reconfigurable artificial cytoskeleton bound to lipid membranes. We also have gone beyond the original aims of the proposal to characterise a model cytoskeleton to work with collaborators (Gadgegaard, Glasgow) to fabricate nanostructure surfaces. This work is in preparation for publication, and will show the roles of topography and topology in controlling diffusive properties of cell membranes. Using these artificial lipid bilayers we have examined the folding mechanism of important proteins of bacterial outer membranes using optical methods with single-molecule resolution.
We have also developed methods to produce double bilayer structures, and work here has focused on characterising the steric effects on protein and peptide assembly in this artificial model of a cellular synapse. A manuscript is in preparation.
We have also completed work characterising methods of pore formation in membrane using single-molecule methods in our artificial bilayers. We have helped shed light on the fundamental principles governing electric field-induced pore formation, and important process used in food sterilisation, genetic modification, and tumour ablation. Similarly, we have studied the mechanism by which antimicrobial peptides induced pores, this work suggests a common mode of action across peptide classes previously thought to be dissimilar.