Spiders Use Structural Conversion of Globular Amyloidogenic Domains to Make Strong Silk Fibers

Over the past two decades, significant advancements have been made in the scalable production and commercialization of microbially‐produced recombinant protein polymers. This perspective presents the evolution from early research efforts to the development of market‐ready products, with a focus on recombinant silk‐like proteins. Initial attempts to synthesize spider silk proteins in microbial hosts faced challenges with solubility, stability, and yield. Recent advancements in synthetic biology, protein engineering, and bioprocess development have enabled the substantial progress on these challenges. Early commercial efforts highlight the complexities and high costs involved in silk production and more recent strategies have shifted toward processes with better scalability, techno‐economics, and product properties. Significant commercial progress has been made, with products launched in textiles and personal care. Although market penetration is limited so far, substantial groundwork is laid for future success. Key challenges remain, such as continued high production costs and the need for cost‐effective purification and fiber spinning techniques. However, the convergence of scientific, technological, and market developments –including a growing number of product launches – suggests that recombinant silk and protein polymers can soon become widespread sustainable materials across various industries.

Current Progress on Scale‐Up and Commercialization of Microbially‐Produced Silk

Breslauer

2024

Unraveling the Molecular Origin of Prey‐Wrapping Spider Silk's Unique Mechanical Properties and Assembly Process Using NMR

Chalek,

Onofrei,

Aldana

et al. 2024

Prey wrapping spider silk's unique mechanical properties are investigated confirming the silk's high degree of extensibility and superior toughness compared to other types of spider silk. For the first time, the pre‐spinning dope phase is studied in isotope‐enriched intact aciniform (AC) silk glands using solution NMR that reveals a combination of α‐helical domains linked by disordered random coil chains consistent with previously proposed “beads‐on‐a‐string” models. The model is further refined through the AlphaFold2 protein structure prediction tool. Finally, extensive magic angle spinning (MAS) solid‐state (SS) NMR data for isotopically‐enriched fibers is used to refine the structural model for AC silk from two species, A. aurantia and A. argentata. The SSNMR data shows that the AC silk fibers are highly α‐helical, coiled‐coil in structure but, also exhibit significant β‐sheet components that can be traced back to the Gly‐rich disordered linker regions in the pre‐spinning dope phase that are converted to β‐sheet structures during fiber formation. This combination of mechanical and structural characterization enhances the understanding of AC silk's liquid‐to‐solid transition and structure‐mechanics relationship. These prey wrap silk results and models will provide the basis for the design of biomimetic materials inspired by the AC spider silk system.

Biomimetic Spider Silk by Crosslinking and Functionalization with Multiarm Polyethylene Glycol

Romaņuks,

Fridmanis,

Schmuck

et al. 2024

Spider silk is renowned for its exceptional mechanical properties, surpassing those of other natural and many synthetic fibers. Yet, replicating its remarkable properties through synthetic production remains a challenge. The variability in the mechanical properties of synthetic spider silks lacking protective coatings, exacerbated by factors such as spinning conditions and humidity levels, poses an additional challenge, impacting their application potential. Bioconjugation offers a versatile synthetic method to modify protein structures, enhancing their pharmacokinetics, solubility, stability, and immune response. In particular, polyethylene glycol (PEG)‐ylation has emerged as a successful strategy with numerous marketed PEG–protein conjugates. This study introduces synthetic spider silk—multiarm PEG bioconjugates, facilitating spidroin crosslinking, and chemical functionalization while retaining a biomimetic spinning approach. Two different examples demonstrate the potential of this approach to improve the fiber's tensile strength and extensibility, respectively, both leading to an increased toughness modulus. Furthermore, the approach could allow the tuning of fiber mechanical properties without developing a new mini‐spidroin construct and fiber coating with lipids attached to multiarm PEG, potentially mitigating the impact of environmental conditions on synthetic spider silk fibers.