Effect of Surface Chemistry on Islet Amyloid Polypeptide Conformation

<div>The formation of dense, linear protein arrays (fibrils) is the hallmark of a number of degenerative</div><div>diseases, such as Alzheimer’s and type-2 diabetes. Protein fibrils have also attracted interest</div><div>as building blocks for new materials. It has long been recognised that surfaces can affect the</div><div>fibrillation process. Recent work on the model fibril forming protein human islet polypeptide</div><div>(hIAPP) has shown that while the protein concentration is highest at hydrophobic surfaces, the</div><div>rate of fibril formation is lower than on other surfaces. To understand this, replica exchange</div><div>molecular dynamics simulations were used to investigate the conformations that hIAPP adopts on</div><div>surfaces of di↵erent hydrophobicity. The hydrophobic surface stabilizes ↵-helical structures, which</div><div>are quite di↵erent to those found on the hydrophilic surface and in bulk solution. There is also</div><div>a greatly reduced conformational ensemble on the hydrophobic surface, due to long-lived contacts</div><div>between hydrophobic residues on the protein and the surface. This new microscopic information</div><div>will help us determine the mechanism of the enhancement of fibril formation on surfaces.</div>

Effect of Surface Chemistry on Islet Amyloid Polypeptide Conformation

<div>The formation of dense, linear protein arrays (fibrils) is the hallmark of a number of degenerative</div><div>diseases, such as Alzheimer’s and type-2 diabetes. Protein fibrils have also attracted interest</div><div>as building blocks for new materials. It has long been recognised that surfaces can affect the</div><div>fibrillation process. Recent work on the model fibril forming protein human islet polypeptide</div><div>(hIAPP) has shown that while the protein concentration is highest at hydrophobic surfaces, the</div><div>rate of fibril formation is lower than on other surfaces. To understand this, replica exchange</div><div>molecular dynamics simulations were used to investigate the conformations that hIAPP adopts on</div><div>surfaces of di↵erent hydrophobicity. The hydrophobic surface stabilizes ↵-helical structures, which</div><div>are quite di↵erent to those found on the hydrophilic surface and in bulk solution. There is also</div><div>a greatly reduced conformational ensemble on the hydrophobic surface, due to long-lived contacts</div><div>between hydrophobic residues on the protein and the surface. This new microscopic information</div><div>will help us determine the mechanism of the enhancement of fibril formation on surfaces.</div>