Molecular simulation of protein adhesion for rational design of antimicrobial surfaces
Creators: name: Ley, Kamron
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 401605
subject: Functional materials
classificationCode: 401807
subject: Nanomaterials
classificationCode: 460207
subject: Modelling and simulation

description: This thesis employs atomistic level modelling to investigate behaviour of surfaces protected through functionalisation with short organic ligands, and their interaction with protein contaminants. A detailed description of the motivation for this project, a detailed literature review on the biofouling process, strategies to prevent biofouling and anti-fouling theory are presented in Chapter 1.<br><br>Classical Molecular Dynamics (MD) techniques are employed to describe the behaviour of our functionalised surfaces in aqueous environments, and the physical interactions with our protein contaminant, EAS hydrophobin. A detailed description of these computational techniques is included in Chapter 2.<br>In Chapter 3, we outline the challenges and limitations of molecular modelling techniques, followed by a detailed background in the development and validation of silica and polyester substrates that have been used in this study. We have also included a detailed description of the computational surface models and surface functionalisation process.<br><br>In order to tailor surfaces for specific applications, the underlying molecular mechanism that enables a functionalised surface to change properties in response to an external trigger must be understood. In Chapter 4 we investigate de-swelling and swelling of some of the most commonly used responsive materials, poly(ethylene glycol) (PEG) functionalised silica and polymer surfaces, as a function of hydration and temperature. We also investigate the difference between the hard (silica) and soft (polyester) substrates, and PEG grafting density on responsive behaviour. We show that enhancement of the surface hardness must be considered when designing responsive surfaces for solution based applications, such as antimicrobial coatings for interchangeable wet/dry environments and biomedicine.<br><br>In Chapter 5, we compare the hydration and chain dynamics of PEG and poly(2-oxazoline) (POX) modified silica surfaces as a function of heterogeneity. We assess how chemistry and surface density of commonly used anti-fouling surface ligands affect the interfacial properties relevant to biofouling. We show how existing theories that attempt to explain underlying molecular mechanisms of biofilm formation and its attenuation are not consistent with experiments, and detail findings that can be exploited in the rational design of biofouling resistant surfaces for industrial and biomedical applications.<br><br>To better understand our protein contaminant, EAS hydrophobin, we study the initial stages of monomeric EAS hydrophobin’s spontaneous adsorption on fully hydroxylated silica. Presented in Chapter 6, a series of MD simulations are undertaken with EAS in solvent only, and also positioned above the silica surface, enabling us to gain a better understanding of EAS’ behaviour in solvent phase, and at interfaces. This allows us to explore the anti-fouling efficacy of PEG and POX surface coatings.<br><br>Combining the detailed knowledge of our surfaces, and the protein, in Chapter 7 we look to elucidate whether entropic barriers associated with surface mobility or those from interfacial water have greater contributions to anti-fouling efficacy. To do this, we simulate the initial stages of the spontaneous adsorption of monomeric EAS hydrophobin on PEG and POX functionalised silica surfaces. From the knowledge gained, we have developed several updated design principles and an updated understanding of anti-fouling surfaces, which we summarise in Chapter 8. Several ideas for continuation of research in anti-fouling surfaces is then presented in the Future Work section.<br>