From assembly to mechanics: predictive scale bridging simulations of spider silk

• Applicant: Professorin Dr. Frauke Gräter
• Subject Area: Synthesis and Properties of Functional Materials ; Biophysics
• Term: from 2011 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 206924251

• Final Report Year: 2022

Final Report Abstract

Biomaterials can feature superior toughness compared to synthetic materials, which is thought to hinge upon the underlying nano-scale structure. Silk is one such protein-based nanostructured biomaterials. It is composed of proteins which self-assemble into nano-scale crystalline beta-sheet stacks surrounded by a matrix of highly disordered silk protein chains. Many previous computational studies, including those by us, were based on a model of silk’s molecular structure. However, such a structure has not been directly measured yet. It is wellknown that the intricate molecular structure inside silk fibers only forms and heavily depends on the presence of flow as present in a spider’s spinning duct. In this funding period, we thus set out to examine the mechanism underlying the self-assembly of silk fibers under flow. We tackled this question bottom-up, starting from an implementation of uniform flow into Molecular Dynamics (MD) simulations within Gromacs. This was followed by a detailed study of the conformational propensity of a silk peptide as a function of flow velocity in atomistic MD simulations. We then moved on to an array of silk peptides under flow, for which we resorted to a coarse-grain model studied by multi-particle collision dynamics (MPCD) simulations to reach the length and time scales required to monitor assembly. As expected, flow stretches the disordered region of silk proteins leading to larger elongations and stronger alignment of the chains along the flow. A key result of our multi-scale study is that this elongation at higher flow rates on one hand slows down the overall rate of assembly between silk peptides as the chains are constrained in the conformational fluctuations, but on the other hand increases the quality of the assembly by promoting beta-sheet formation. The underlying mechanism is that at high flow rates, chains show higher rates for both contact formation and dissociation, rendering the assembly reversible and allowing for the formation of more low-energy assemblies. We expect these results to be an important step forward towards redesigning the intricate coupling between assembly, structure, and mechanics of silk and potentially other nanoscale biomaterials.

Publications

• Molecular Dynamics Simulations of Molecules in Uniform Flow. Biophysical Journal, 116(9), 1579-1585.
  Herrera-Rodríguez, Ana M.; Miletić, Vedran; Aponte-Santamaría, Camilo & Gräter, Frauke
  
• Phosphorylation tunes elongation propensity and cohesiveness of INCENP’s intrinsically disordered region. Journal of Molecular Biology, 434(1), 167387.
  Martin, Isabel M.; Aponte-Santamaría, Camilo; Schmidt, Lisa; Hedtfeld, Marius; Iusupov, Adel; Musacchio, Andrea & Gräter, Frauke
  
• The role of hydrodynamic flow in the self-assembly of dragline spider silk proteins. Cold Spring Harbor Laboratory.
  Herrera-Rodríguez, Ana M.; Dasanna, Anil Kumar; Daday, Csaba; Cruz-Chú, Eduardo R.; Aponte-Santamaría, Camilo; Schwarz, Ulrich S. & Gräter, Frauke