Predicting Silk Fiber Mechanical Properties through Multiscale Simulation and Protein Design

Abstract

Silk is a promising material for biomedical applications, and much research is focused on how application-specific, mechanical properties of silk can be designed synthetically through proper amino acid sequences and processing parameters. This protocol describes an iterative process between research disciplines that combines simulation, genetic synthesis, and fiber analysis to better design silk fibers with specific mechanical properties. Computational methods are used to assess the protein polymer structure as it forms an interconnected fiber network through shearing and how this process affects fiber mechanical properties. Model outcomes are validated experimentally with the genetic design of protein polymers that match the simulation structures, fiber fabrication from these polymers, and mechanical testing of these fibers. Through iterative feedback between computation, genetic synthesis, and fiber mechanical testing, this protocol will enable a priori prediction capability of recombinant material mechanical properties via insights from the resulting molecular architecture of the fiber network based entirely on the initial protein monomer composition. This style of protocol may be applied to other fields where a research team seeks to design a biomaterial with biomedical application-specific properties. This protocol highlights when and how the three research groups (simulation, synthesis, and engineering) should be interacting to arrive at the most effective method for predictive design of their material.

A supertough electro-tendon based on spider silk composites

“…To understand how SWCNT improve the mechanical properties of S-silk at the microscopic scale, DPD simulation was performed. Here we adopted a coarse-grained description 43,44 of silk proteins and SWCNT to investigate the structural evolution of amorphous (3 1helix and β-turn) and crystalline (β-sheet nanocrystal) structures of silk in the presence of SWCNT under different strains. Every 9 water molecules are represented by one hydrophilic "w" bead, as shown in Supplementary Fig.…”

Revealing Spider Silk's 3D Nanostructure Through Low Temperature Plasma Etching and Advanced Low-Voltage SEM

“…These properties are attributed to a hierarchical arrangement of ordered and disordered protein structures within a single fiber (Vollrath and Porter, 2009;Vollrath et al, 2011;Porter et al, 2013). This nanostructure has been extensively explored by bulk and space-averaging techniques such as calorimetry (Cebe et al, 2013;Vollrath et al, 2014;Holland et al, 2018a), spectroscopy (Dicko et al, 2007;Boulet-Audet et al, 2015) small angle scattering X-ray and neutron diffraction (Termonia, 1994;Riekel et al, 2000;Greving et al, 2010;Wagner et al, 2017) and solid state nuclear magnetic resonance (NMR) (Willis et al, 1972;Hijirida et al, 1996;Kümmerlen et al, 1996;Yang et al, 2000;Holland et al, 2008;McGill et al, 2018), which together have provided the fuel for a range of modeling approaches (Giesa et al, 2011;Cranford, 2013;Ebrahimi et al, 2015;Rim et al, 2017). In comparison, spatially resolved techniques are yet to be fully explored, but have already hinted at a diverse set of rich nano-and microscale features such as micelles (Lin et al, 2017;Oktaviani et al, 2018;Parent et al, 2018), nanofibrils (Wang and Schniepp, 2018), elongated cavities (Frische et al, 2002), and an overall radial variation of composition and structure (Li et al, 1994;Knight et al, 2000;Frische et al, 2002;Sponner et al, 2007;Brown et al, 2011).…”

Multiscale Modeling of Silk and Silk‐Based Biomaterials—A Review

“…Thus, using different modeling and simulation techniques, we are able to design these materials along different length scales, from the amino acid sequence to the macroscopic structure, to predict their properties . These in silico approaches can enormously reduce the costs of experimental research . Many of these bottom‐up models for silk and silk‐based biomaterials have been extensively validated by experiments, showcasing their predictive power …”

“…In this regard, computational modeling at different length scales provides fundamental understanding of structure–property and sequence–property relationships that can greatly accelerate the development of novel silk structures and silk‐based materials with tailored specific properties . Nevertheless, these computational models must also be validated and improved by iterating between simulations and experimental research on the synthesis and processing of silk biopolymers . The requirement of such iterative process highlights the need for interdisciplinary research consortia to accelerate the development of silk into a mainstream feedstock in the materials industry.…”