Fibril Assembly Amyloid Nature of Silk

Spinning Versus Growth Length and Time Scale Change 

The forces that stabilize amyloid fibrils include specific hydrogen bonding, electrostatic interactions, n-n stacking, and hydrophobic interactions. Importantly, similar types of interactions stabilize the functional native structures of protein molecules (Anfinsen, 1973 Dill, 1990 Dobson and Karplus, 1999 Kauzmann, 1959). In this sense, the conditions that favor native protein folding might also be manipulated to facilitate the formation of amyloid fibrils. 

It is now well understood that fibril formation requires conformational changes, but the assembly steps may differ from one system to another (Kelly, 1998). For example, aggregation into well-ordered structures occurs in multiple steps during the formation of /Mactoglobulin fibrils. First, there is a fast and reversible step followed by an irreversible step involving the formation of nonreversible /1-sheet structures (Arnaudov et al., 2003). Interestingly, the reversible step, which corresponds to a lag in fibril formation, varies from one system to another and most likely depends on the specific kinetic partitioning between the misfolded intermediate and the native state (Dobson, 1999 Jaenicke, 1995 Uversky, 2003). 

The model of amyloid fibril formation is a nucleation step followed by growth, where the nucleation mechanism dictates the concentration and time dependence of the aggregation (Harper and Lansbury, 1997  

Lomakin et al., 1996). Surface plasmon resonance studies of the A/ (l—40) /1-amyloid peptide (Cannon et al., 2004) provide even more details of the multiple kinetic steps, and suggest that fibril formation proceeds by reversible addition of a monomer to the tip of the formed fibril, followed by a postbinding, transitional event. 

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