Flow-Induced Self-Assembly of Spider Silk from Multi-Scale Simulations

Abstract

Dragline spider silk proteins or spidroins self-assemble into an outstandingly tough fiber. The combination of ductility and strength relies in its microscopic structure within the fiber: small and strong beta-sheet crystals formed by poly-alanine repeats embedded into a flexible amorphous matrix of glycine-rich repeats. Flow is a critical factor for the assembly of the highly disordered silk proteins into this elaborated structure within the fibril. However, the mechanism of flow-induced silk self-assembly remains elusive. We studied oligomer formation of tethered repetitive dragline peptides under uniform flow using non-equilibrium multi-scale molecular dynamics simulations at different flow rates. In atomistic Molecular Dynamics simulations, we found poly-alanine repeats to primarily drive the self-assembly, confirming crystal formation to promote fibrillation. We used this finding in more coarse-grained hydrodynamic simulations with aminoacid resolution, treating the silk proteins as semi-flexible block copolymers. We observed that medium to high flow velocities (>20 cm/s) increase alignment and crystallization of the silk peptides. High velocities (> 50 cm/s) result in extensions close to the contour length of the protein (>90%), thereby slowing down the assembly process as protein fluctuations are largely abolished. Our results yield a microscopic understanding of flow-induced silk assembly, which is likely relevant also for other flow-dependent proteins.