Thesis
Understanding lipid bilayer disruption by antimicrobial monoglycerides using molecular dynamics simulations
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2026
- Thesis identifier
- T18174
- Person Identifier (Local)
- 202252412
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Monoglycerides are glycerol-fatty acid esters of which several molecules, in particular those of medium-chain length, have well documented antimicrobial potency, making them a promising research area for potential future disinfectants and antimicrobials. The antimicrobial mechanisms of monoglycerides have been extensively researched using experimental approaches, identifying that a key aspect to their potency is the ability to insert into and disrupt the biological membranes found in bacterial cells, inhibiting membrane-associated processes and cause changes to membrane properties and structure. Due to the small scale size of individual MG molecules, it is difficult to assess some aspects of this mechanism using current experimental methods, creating a need to utilise computational techniques to simulate monoglyceride behaviour within biological membranes in order to further characterise their disruption mechanisms and address current gaps in knowledge. The research employed in this thesis aims to fill this knowledge gap by utilising all-atom Molecular Dynamics simulations to explore monoglyceride interactions with lipid bilayers at an atomistic level of detail. In the first phase of research presented in this thesis a series of simulations was created using a simplified lipid bilayer system and a variety of MGs set up in ideal conditions for examining experimental hypotheses regarding monoglyceride behaviour, providing novel evidence that bilayer disruption is disproportionately higher at high monoglyceride concentrations, that at equal monoglyceride concentrations within a bilayer the monoglyceride C8-MG causes more significant disruption than monoglycerides C10-MG and C12-MG, and that asymmetric monoglyceride distributions across leaflets cause significantly more disruption. The second phase of research repeated this methodology with more complex bilayer models closer replicating bacterial membranes, confirming that bilayer composition affects membrane susceptibility to monoglycerides, though trends from the simplified system remained consistent. Potential bilayer stress relief mechanisms from asymmetric monoglyceride concentrations in the form of monoglyceride flip-flop and leaflet budding were also identified. Finally, free energy barriers to monoglyceride movement through lipid bilayer systems were calculated using umbrella sampling, identifying negligible energy barriers for monoglyceride entry from the water box into cell membranes. Expected timescales for monoglycerides to remain in lipid bilayers were calculated, revealing C12-MG to be the more stable in a leaflet than C8-MG and C10-MG. Energy barriers to monoglyceride movement were also shown to differ based on bilayer composition, and prior disruption of a leaflet by monoglycerides does not lower the energy barriers required for monoglyceride entry, but may lower the free energy barriers for MGs to move within the bilayer system. The findings presented within this thesis can be used to evaluate existing experimental hypotheses regarding bilayer disruption, as well as highlight the importance and utility of molecular dynamics methodologies as a tool to complement experimental research. The groundwork laid in this thesis provides clear avenues to build upon utilising molecular dynamics simulations in order to further investigate the antimicrobial applications of monoglycerides and produce a strong overall picture of how they can be used for real-world applications in agriculture and healthcare.
- Advisor / supervisor
- Ferro, Valerie A.
- Kelemen, Donald
- Mulheran, Paul A.
- Kubiak-Ossowska, Karina
- Resource Type
- DOI
- Funder
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PDF of thesis T18174 | 2026-09-30 | Public | Download |