Dynamics and Control of Peptide Self-Assembly and Aggregation

Abstract

The aggregation of proteins into fibrillar structures is a central process implicated in the onset and development of several devastating neuro-degenerative diseases, but can, in contrast to these pathological roles, also fulfil important biological functions. In both scenarios, an understanding of the mechanisms by which soluble proteins convert to their fibrillar forms represents a fundamental objective for molecular sciences. This chapter details the different classes of microscopic processes responsible for this conversion and discusses how they can be described by a mathematical formulation of the aggregation kinetics. We present easily accessible experimental quantities that allow the determination of the dominant pathways of aggregation, as well as a general strategy to obtain detailed solutions to the kinetic rate laws that yield the microscopic rate constants of the individual processes of nucleation and growth. This chapter discusses a framework for a structured approach to address key questions regarding the dynamics of protein aggregation and shows how the use of chemical kinetics to tackle complex biophysical systems can lead to a deeper understanding of the underlying physical and chemical principles.