The effects of model membrane complexity for the E.coli cell envelope

Abstract

To overcome resistance to antibiotics in bacteria, such as Escherichia coli, further understanding of the nature of the cell envelope is required. Molecular dynamics has provided a powerful tool into investigations of the dynamics and structure of biological systems of varying complexity. In this thesis, coarse-grained simulations were used to probe the behaviour of the outer membrane and the proteins within, relative to typical phospholipid membranes. In the first chapter, nanopores of varying sizes, shapes and chemistry were studied in the context of symmetric and asymmetric bacterial membranes. It was found that communication between leaflets played a significant role in lipid sorting of larger lipids. Following this, a broad study of the protein-lipid interactions between a range of different proteins and outer membrane models was carried out. The interactions between a protein and any given outer membrane model were found to have a unique fingerprint. The stability of the lipids in outer and inner membranes were then investigated by measuring the free energy of lipid extraction. The results concluded that there was little similarity between the extraction of different lipopolysaccharide lipids, as well as repeats of the same lipid. A further study on the effects of a membrane protein on the stability of local and bulk lipids was carried out for the inner membrane. In the final chapter, the use of sparse lipopolysaccharide densities and Hamiltonian Replica Exchange Molecular Dynamics were investigated to enhance lipopolysaccharide mixing.

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ORCID for Syma Khalid: orcid.org/0000-0002-3694-5044

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