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Mechanism, scaling and rates of protein aggregation from in vivo measurements

The formation and proliferation of protein aggregates play a central role in a number of devastating neuro-degenerative diseases. Many experimental studies indicate that the ability of existing aggregates to replicate is a key property in generating their pathogenic effect across a range of diseases. However, given the complexity of the process in vivo, no principled general approach currently exists to obtain the rates of the fundamental steps that underlie aggregate formation from measurements in living systems. In order to address this challenge, here we present a general approach for analysing aggregation kinetics that considers broad classes of processes that can be described by a family of scaling solutions. Our approach is not limited only to fibrillar aggregates, but applies to any aggregate shape. We show that the rates can reliably be extracted by fitting of a simple logistic function, even from experimental data in living systems, and give a very general analytical expression that relates the scaling of the exponential rate with monomer concentration to the microscopic details of the underlying reaction. This approach can thus be used to infer the microscopic mechanism driving the aggregation process from macroscopic measurements in complex systems.