Conference Contribution Details
Mandatory Fields
Cheung, David L.
FEBS Advanced Lecture Course 'Biological Surfaces and Interfaces'
Effect of surface structure and chemistry on protein conformation
Sant Feliu de Guixols, Spain
Oral Presentation
Optional Fields
30-JUN-19
05-JUL-19
Understanding the adsorption of proteins onto material surfaces is a major challenge in the design of biomaterials for medical applications and in the creation of nanostructured materials from protein building blocks. Understanding the behaviour of proteins at surfaces on a microscopic level requires insight into the interplay between a range of different effects, including the surface chemistry and structure and protein sequence. Protein behaviour at surfaces involves processes that occur on short length and timescales making experimental investigation of this challenging. As molecular simulation operates directly at the microscopic length scales it is well-suited to provide molecular-level, mechanistic detail on protein adsorption and function of surfaces. In this presentation recent work using molecular dynamics simulations to investigate the effect of surface properties on protein conformation will be described. Simulation of model peptides (LKpeptides) on nanostructured surfaces, consisting of alternating hydrophilic and hydrophobic stripes, are used to investigate the role of surface structure on protein adsorption. The strongest adsorption is found for surfaces with larger hydrophobic regions, as the peptides can minimise unfavourable contacts with hydrophilic regions of the surface. Changes to the conformational entropy of the peptides during adsorption are shown to play an important role in controlling the adsorption strength, with differences between the peptides appearing for narrow stripes. The role of surface hydrophobicity on the conformation of an intrinsically disordered protein, islet amyloid polypeptide (IAPP), is also investigated. On hydrophobic surfaces the protein tends to adopt more structured conformations compared to polar surfaces and in bulk solution. The differing structures adopted by IAPP on these different surfaces can be used to rationalise experimental observations of IAPP fibrillation. This information may be used to understand how the adsorption of proteins is related to the surface properties, allowing for control over biocompatibility and anti-fouling behaviour, and control over the formation of protein nanostructures on surfaces.
Publication Themes