Amino acid-dependent phase equilibrium and material properties of tetrapeptide condensates

The rules of how amino acids dictate the physical properties of biomolecular condensates are still incomplete. Here, we study condensates formed by tetrapeptides of the form XXssXX. Eight peptides form four types of condensates at different concentrations and pHs: droplets (X = F, L, M, P, V, and A), amorphous dense liquids (X = L, M, P, V, and A), amorphous aggregates (X = W), and gels (X = I, V, and A). The peptides exhibit differences in phase equilibrium and material properties, including a 368-fold range in the threshold concentration for phase separation and a 3,856-fold range in viscosity. All-atom molecular dynamics simulations provide physical explanations of these results. The present work also reveals widespread critical behaviors-including critical slowing down manifested by amorphous dense liquids and critical scaling obeyed by fusion speed-with broad implications for condensate functions.