Glucagon stop-go kinetics supports a monomer-trimer fibrillation model

Abstract

We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at various concentrations using confocal microscopy and determine the glucagon fibril persistence length $60 \mu\textrm{m}$. At all concentrations we observe that periods of individual fibril growth are interrupted by periods of stasis. The growth probability is large at high and low concentrations and is reduced for intermediate glucagon concentrations. To explain this behavior we propose a simple model, where fibrils come in two forms, one built entirely from glucagon monomers and one entirely from glucagon trimers. The opposite building blocks act as fibril growth blockers, and this generic model reproduces experimental behavior well.