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Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural designs to discover proteins that meet specified mechanical properties remains challenging. Here, we report a generative model that predicts protein designs to meet complex nonlinear mechanical property-design objectives. Our model leverages deep knowledge on protein sequences from a pretrained protein language model and maps mechanical unfolding responses to create proteins. Via full-atom molecular simulations for direct validation, we demonstrate that the designed proteins are de novo, and fulfill the targeted mechanical properties, including unfolding energy and mechanical strength, as well as the detailed unfolding force-separation curves. Our model offers rapid pathways to explore the enormous mechanobiological protein sequence space unconstrained by biological synthesis, using mechanical features as the target to enable the discovery of protein materials with superior mechanical properties.

Biomineralization is a common strategy used in Nature to improve the mechanical strength and toughness of biological materials. This strategy, applied in materials like bone or nacre, serves as inspiration for materials scientists and engineers to design new materials for applications in healthcare, soft robotics or the environment. In this regard, composites consisting of silk and hydroxyapatite have been extensively researched for bone regeneration applications, due to their reported cytocompatibility and osteoinduction capacity that supports bone formation in vivo . Thus, it becomes relevant to understand how silk and hydroxyapatite interact at their interface, and how this affects the overall mechanical properties of these composites. This theoretical-experimental work investigates the interfacial dynamic and structural properties of silk in contact with hydroxyapatite, combining molecular dynamics simulations with analytical characterization. Our data indicate that hydroxyapatite decreases the β-sheets in silk, which are a key load-bearing element of silk. The β-sheets content can usually be increased in silk biomaterials via post-processing methods, such as water vapor annealing. However, the presence of hydroxyapatite appears to reduce also for the formation of β-sheets via water vapor annealing. This work sheds light into the interfacial properties of silk-hydroxyapatite composite and their relevance for the design of composite biomaterials for bone regeneration.

Spiders are nature's engineers that build lightweight and high-performance web architectures often several times their size and with very few supports; however, little is known about web mechanics and geometries throughout construction, especially for three-dimensional (3D) spider webs. In this work, we investigate the structure and mechanics for a Tidarren sisyphoides spider web at varying stages of construction. This is accomplished by imaging, modeling, and simulations throughout the web-building process to capture changes in the natural web geometry and the mechanical properties. We show that the foundation of the web geometry, strength, and functionality is created during the first 2 d of construction, after which the spider reinforces the existing network with limited expansion of the structure within the frame. A better understanding of the biological and mechanical performance of the 3D spider web under construction could inspire sustainable robust and resilient fiber networks, complex materials, structures, scaffolding, and self-assembly strategies for hierarchical structures and inspire additive manufacturing methods such as 3D printing as well as inspire artistic and architectural and engineering applications., Competing Interests: The authors declare no competing interest.

Silk embodies outstanding material properties and biologically relevant functions achieved through a delicate hierarchical structure. It can be used to create high-performance, multifunctional, and biocompatible materials through mild processes and careful rational material designs. To achieve this goal, computational modeling has proven to be a powerful platform to unravel the causes of the excellent mechanical properties of silk, to predict the properties of the biomaterials derived thereof, and to assist in devising new manufacturing strategies. Fine-scale modeling has been done mainly through all-atom and coarse-grained molecular dynamics simulations, which offer a bottom-up description of silk. In this work, a selection of relevant contributions of computational modeling is reviewed to understand the properties of natural silk, and to the design of silk-based materials, especially combined with experimental methods. Future research directions are also pointed out, including approaches such as 3D printing and machine learning, that may enable a high throughput design and manufacturing of silk-based biomaterials., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Silk-elastin-like-protein polymers (SELPs) are genetically engineered recombinant protein sequences consisting of repeating units of silk-like and elastin-like blocks. By combining these entities, it is shown that both the characteristic strength of silk and the temperature-dependent responsiveness of elastin can be leveraged to create an enhanced stimuli-responsive material. It is hypothesized that SELP behavior can be influenced by varying the silk-to-elastin ratio. If the responsiveness of the material at different ratios is significantly different, this would allow for the design of materials with specific temperature-based swelling and mechanical properties. This study demonstrates that SELP fiber properties can be controlled via a temperature transition dependent on the ratio of silk-to-elastin in the material. SELP fibers are experimentally wet spun from polymers with different ratios of silk-to-elastin and conditioned in either a below or above transition temperature (T t ) water bath prior to characterization. The fibers with higher elastin content showed more stimuli-responsive behavior compared to the fibers with lower elastin content in the hot (57-60 °C) versus cold (4-7 °C) environment, both computationally and experimentally. This work builds a foundation for developing SELP materials with well-characterized mechanical properties and responsive features., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Spiders are abundantly found in nature and most ecosystems, making up more than 47 000 species. This ecological success is in part due to the exceptional mechanics of the spider web, with its strength, toughness, elasticity and robustness, which originate from its hierarchical structures all the way from sequence design to web architecture. It is a unique example in nature of high-performance material design. In particular, to survive in different environments, spiders have optimized and adapted their web architecture by providing housing, protection, and an efficient tool for catching prey. The most studied web in literature is the two-dimensional (2D) orb web, which is composed of radial and spiral threads. However, only 10% of spider species are orb-web weavers, and three-dimensional (3D) webs, such as funnel, sheet or cobwebs, are much more abundant in nature. The complex spatial network and microscale size of silk fibres are significant challenges towards determining the topology of 3D webs, and only a limited number of previous studies have attempted to quantify their structure and properties. Here, we focus on developing an innovative experimental method to directly capture the complete digital 3D spider web architecture with micron scale resolution. We built an automatic segmentation and scanning platform to obtain high-resolution 2D images of individual cross-sections of the web that were illuminated by a sheet laser. We then developed image processing algorithms to reconstruct the digital 3D fibrous network by analysing the 2D images. This digital network provides a model that contains all of the structural and topological features of the porous regions of a 3D web with high fidelity, and when combined with a mechanical model of silk materials, will allow us to directly simulate and predict the mechanical response of a realistic 3D web under mechanical loads. Our work provides a practical tool to capture the architecture of sophisticated 3D webs, and could lead to studies of the relation between architecture, material and biological functions for numerous 3D spider web applications., (© 2018 The Author(s).)

Tensan silk, a natural fiber produced by the Japanese oak silk moth ( Antherea yamamai, abbreviated to A. yamamai), features superior characteristics, such as compressive elasticity and chemical resistance, when compared to the more common silk produced from the domesticated silkworm, Bombyx mori ( B. mori). In this study, the "structure-property" relationships within A. yamamai silk are disclosed from the different structural hierarchies, confirming the outstanding toughness as dominated by the distinct mesoscale fibrillar architectures. Inspired by this hierarchical construction, we fabricated A. yamamai silk-like regenerated B. mori silk fibers (RBSFs) with mechanical properties (extensibility and modulus) comparable to natural A. yamamai silk. These RBSFs were further functionalized to form conductive RBSFs that were sensitive to force and temperature stimuli for applications in smart textiles. This study provides a blueprint in exploiting rational designs from A. yamanmai, which is rare and expensive in comparison to the common and cost-effective B. mori silk to empower enhanced material properties.

Spider dragline silk is a protein material that has evolved over millions of years to achieve finely tuned mechanical properties. A less known feature of some dragline silk fibers is that they shrink along the main axis by up to 50% when exposed to high humidity, a phenomenon called supercontraction. This contrasts the typical behavior of many other materials that swell when exposed to humidity. Molecular level details and mechanisms of the supercontraction effect are heavily debated. Here we report a molecular dynamics analysis of supercontraction in Nephila clavipes silk combined with in situ mechanical testing and Raman spectroscopy linking the reorganization of the nanostructure to the polar and charged amino acids in the sequence. We further show in our in silico approach that point mutations of these groups not only suppress the supercontraction effect, but even reverse it, while maintaining the exceptional mechanical properties of the silk material. This work has imminent impact on the design of biomimetic equivalents and recombinant silks for which supercontraction may or may not be a desirable feature. The approach applied is appropriate to explore the effect of point mutations on the overall physical properties of protein based materials.

Tailored biomaterials with tunable functional properties are crucial for a variety of task-specific applications ranging from healthcare to sustainable, novel bio-nanodevices. To generate polymeric materials with predictive functional outcomes, exploiting designs from nature while morphing them toward non-natural systems offers an important strategy. Silks are Nature's building blocks and are produced by arthropods for a variety of uses that are essential for their survival. Due to the genetic control of encoded protein sequence, mechanical properties, biocompatibility, and biodegradability, silk proteins have been selected as prototype models to emulate for the tunable designs of biomaterial systems. The bottom up strategy of material design opens important opportunities to create predictive functional outcomes, following the exquisite polymeric templates inspired by silks. Recombinant DNA technology provides a systematic approach to recapitulate, vary, and evaluate the core structure peptide motifs in silks and then biosynthesize silk-based polymers by design. Post-biosynthesis processing allows for another dimension of material design by controlled or assisted assembly. Multiscale modeling, from the theoretical prospective, provides strategies to explore interactions at different length scales, leading to selective material properties. Synergy among experimental and modeling approaches can provide new and more rapid insights into the most appropriate structure-function relationships to pursue while also furthering our understanding in terms of the range of silk-based systems that can be generated. This approach utilizes nature as a blueprint for initial polymer designs with useful functions (e.g., silk fibers) but also employs modeling-guided experiments to expand the initial polymer designs into new domains of functional materials that do not exist in nature. The overall path to these new functional outcomes is greatly accelerated via the integration of modeling with experiment. In this Account, we summarize recent advances in understanding and functionalization of silk-based protein systems, with a focus on the integration of simulation and experiment for biopolymer design. Spider silk was selected as an exemplary protein to address the fundamental challenges in polymer designs, including specific insights into the role of molecular weight, hydrophobic/hydrophilic partitioning, and shear stress for silk fiber formation. To expand current silk designs toward biointerfaces and stimuli responsive materials, peptide modules from other natural proteins were added to silk designs to introduce new functions, exploiting the modular nature of silk proteins and fibrous proteins in general. The integrated approaches explored suggest that protein folding, silk volume fraction, and protein amino acid sequence changes (e.g., mutations) are critical factors for functional biomaterial designs. In summary, the integrated modeling-experimental approach described in this Account suggests a more rationally directed and more rapid method for the design of polymeric materials. It is expected that this combined use of experimental and computational approaches has a broad applicability not only for silk-based systems, but also for other polymer and composite materials.

Quantifying the deformation of biological tissues under mechanical loading is crucial to understand its biomechanical response in physiological conditions and important for designing materials and treatments for biomedical applications. However, strain measurements for biological tissues subjected to large deformations and humid environments are challenging for conventional methods due to several limitations such as strain range, boundary conditions, surface bonding and biocompatibility. Here we propose the use of silk solutions and printing to synthesize prototype strain gauges for large strain measurements in biological tissues. The study shows that silk-based strain gauges can be stretched up to 1300% without failure, which is more than two orders of magnitude larger than conventional strain gauges, and the mechanics can be tuned by adjusting ion content. We demonstrate that the printing approach can accurately provide well bonded fluorescent features on the silk membranes using designs which can accurately measure strain in the membrane. The results show that these new strain gauges measure large deformations in the materials by eliminating the effects of sliding from the boundaries, making the measurements more accurate than direct outputs from tensile machines.

We report a new ultrathin filtration membrane prepared from silk nanofibrils (SNFs), directly exfoliated from natural Bombyx mori silk fibers to retain structure and physical properties. These membranes can be prepared with a thickness down to 40 nm with a narrow distribution of pore sizes ranging from 8 to 12 nm. Typically, 40 nm thick membranes prepared from SNFs have pure water fluxes of 13 000 L h(-1) m(-2) bar(-1), more than 1000 times higher than most commercial ultrathin filtration membranes and comparable with the highest water flux reported previously. The commercial membranes are commonly prepared from polysulfone, poly(ether sulfone), and polyamide. The SNF-based ultrathin membranes exhibit efficient separation for dyes, proteins, and colloids of nanoparticles with at least a 64% rejection of Rhodamine B. This broad-spectrum filtration membrane would have potential utility in applications such as wastewater treatment, nanotechnology, food industry, and life sciences in part due to the protein-based membrane polymer (silk), combined with the robust mechanical and separation performance features.

Spiders spin their silk from an aqueous solution to a solid fiber in ambient conditions. However, to date, the assembly mechanism in the spider silk gland has not been satisfactorily explained. In this paper, we use molecular dynamics simulations to model Nephila clavipes MaSp1 dragline silk formation under shear flow and determine the secondary structure transitions leading to the experimentally observed fiber structures. While no experiments are performed on the silk fiber itself, insights from this polypeptide model can be transferred to the fiber scale. The novelty of this study lies in the calculation of the shear stress (300-700 MPa) required for fiber formation and identification of the amino acid residues involved in the transition. This is the first time that the shear stress has been quantified in connection with a secondary structure transition. By study of molecules containing varying numbers of contiguous MaSp1 repeats, we determine that the smallest molecule size giving rise to a "silk-like" structure contains six polyalanine repeats. Through a probability analysis of the secondary structure, we identify specific amino acids that transition from α-helix to β-sheet. In addition to portions of the polyalanine section, these amino acids include glycine, leucine, and glutamine. The stability of β-sheet structures appears to arise from a close proximity in space of helices in the initial spidroin state. Our results are in agreement with the forces exerted by spiders in the silking process and the experimentally determined global secondary structure of spidroin and pulled MaSp1 silk. Our study emphasizes the role of shear in the assembly process of silk and can guide the design of microfluidic devices that attempt to mimic the natural spinning process and predict molecular requirements for the next generation of silk-based functional materials.

Scalable computational modelling tools are required to guide the rational design of complex hierarchical materials with predictable functions. Here, we utilize mesoscopic modelling, integrated with genetic block copolymer synthesis and bioinspired spinning process, to demonstrate de novo materials design that incorporates chemistry, processing and material characterization. We find that intermediate hydrophobic/hydrophilic block ratios observed in natural spider silks and longer chain lengths lead to outstanding silk fibre formation. This design by nature is based on the optimal combination of protein solubility, self-assembled aggregate size and polymer network topology. The original homogeneous network structure becomes heterogeneous after spinning, enhancing the anisotropic network connectivity along the shear flow direction. Extending beyond the classical polymer theory, with insights from the percolation network model, we illustrate the direct proportionality between network conductance and fibre Young's modulus. This integrated approach provides a general path towards de novo functional network materials with enhanced mechanical properties and beyond (optical, electrical or thermal) as we have experimentally verified.

Spiders spin intricate webs that serve as sophisticated prey-trapping architectures that simultaneously exhibit high strength, elasticity and graceful failure. To determine how web mechanics are controlled by their topological design and material distribution, here we create spider-web mimics composed of elastomeric filaments. Specifically, computational modelling and microscale 3D printing are combined to investigate the mechanical response of elastomeric webs under multiple loading conditions. We find the existence of an asymptotic prey size that leads to a saturated web strength. We identify pathways to design elastomeric material structures with maximum strength, low density and adaptability. We show that the loading type dictates the optimal material distribution, that is, a homogeneous distribution is better for localized loading, while stronger radial threads with weaker spiral threads is better for distributed loading. Our observations reveal that the material distribution within spider webs is dictated by the loading condition, shedding light on their observed architectural variations.

Bioengineered spider silk block copolymers were studied to understand the effect of protein chain length and sequence chemistry on the formation of secondary structure and materials assembly. Using a combination of in vitro protein design and assembly studies, we demonstrate that silk block copolymers possessing multiple repetitive units self-assemble into lamellar microstructures. Additionally, the study provides insights into the assembly behavior of spider silk block copolymers in concentrated salt solutions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Millions of years of evolution have adapted spider webs to achieve a range of properties, including the well-known capture of prey, with efficient use of materials. One feature that remains poorly understood is the attachment disc, a network of silk fibers that mechanically anchors a web to its environment. Experimental observations suggest that one possible attachment disc adheres to a substrate through multiple symmetrically branched structures composed of sub-micrometer scale silk fibers. Here, a theoretical model is used to explore the adaptation of the strength of attachment of such an anchorage, and complementary mesoscale simulations are applied to demonstrate a novel mechanism of synergetic material and structural optimization, such that the maximum anchorage strength can be achieved regardless of the initial anchor placement or material type. The optimal delamination (peeling) angle is facilitated by the inherent extensibility of silk, and is attained automatically during the process of delamination. This concept of self-optimizing peeling angle suggests that attachment discs do not require precise placement by the spider, irrespective of adhesion strength. Additional hierarchical branching of the anchorage increases efficiency, where both the delamination force and toughness modulus increase with a splitting of the cross-sectional area., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Among a myriad of spider web geometries, the orb web presents a fascinating, exquisite example in architecture and evolution. Orb webs can be divided into two categories according to the capture silk used in construction: cribellate orb webs (composed of pseudoflagelliform silk) coated with dry cribellate threads and ecribellate orb webs (composed of flagelliform silk fibres) coated by adhesive glue droplets. Cribellate capture silk is generally stronger but less-extensible than viscid capture silk, and a body of phylogenic evidence suggests that cribellate capture silk is more closely related to the ancestral form of capture spiral silk. Here, we use a coarse-grained web model to investigate how the mechanical properties of spiral capture silk affect the behaviour of the whole web, illustrating that more elastic capture spiral silk yields a decrease in web system energy absorption, suggesting that the function of the capture spiral shifted from prey capture to other structural roles. Additionally, we observe that in webs with more extensible capture silk, the effect of thread strength on web performance is reduced, indicating that thread elasticity is a dominant driving factor in web diversification.

Many fibers in biomaterials such as tendon, elastin, or silk feature a nonlinear stiffening behavior of the stress-strain relationship, where the rigidity of the material increases severely as the material is being stretched. Here we show that such nonlinear stiffening is beneficial for a fiber's ability to withstand cracks, leading to a flaw tolerant state in which stress concentrations around cracks are diminished. Our findings, established by molecular mechanics and the derivation of a theoretical scaling law, explain experimentally observed fiber sizes in a range of biomaterials and point to the importance of nonlinear stiffening to enhance their fracture properties. Our study suggests that nonlinear stiffening provides a mechanism by which nanoscale mechanical properties can be scaled up, providing a means towards bioinspired fibrous material and structural design.

Spider silk is a self-assembling biopolymer that outperforms many known materials in terms of its mechanical performance despite being constructed from simple and inferior building blocks. While experimental studies have shown that the molecular structure of silk has a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies in particular under variations of genetic sequences have been reported. Here we report atomistic-level structures of the MaSp1 protein from the Nephila Clavipes spider dragline silk sequence, obtained using an in silico approach based on replica exchange molecular dynamics (REMD) and explicit water molecular dynamics. We apply this method to study the effects of a systematic variation of the poly-alanine repeat lengths, a parameter controlled by the genetic makeup of silk, on the resulting molecular structure of silk at the nanoscale. Confirming earlier experimental and computational work, a structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly β-sheet crystal domains while disorderly regions are formed by glycine-rich repeats that consist of 3(10)-helix type structures and β-turns. Our predictions are directly validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots combined with an analysis of the secondary structure content. The key result of our study is our finding of a strong dependence of the resulting silk nanostructure depending on the poly-alanine length. We observe that the wildtype poly-alanine repeat length of six residues defines a critical minimum length that consistently results in clearly defined β-sheet nanocrystals. For poly-alanine lengths below six, the β-sheet nanocrystals are not well-defined or not visible at all, while for poly-alanine lengths at and above six, the characteristic nanocomposite structure of silk emerges with no significant improvement of the quality of the β-sheet nanocrystal geometry. We present a simple biophysical model that explains these computational observations based on the mechanistic insight gained from the molecular simulations. Our findings set the stage for understanding how variations in the spidroin sequence can be used to engineer the structure and thereby functional properties of this biological superfiber, and present a design strategy for the genetic optimization of spidroins for enhanced mechanical properties. The approach used here may also find application in the design of other self-assembled molecular structures and fibers and in particular biologically inspired or completely synthetic systems., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Natural materials are renowned for exquisite designs that optimize function, as illustrated by the elasticity of blood vessels, the toughness of bone and the protection offered by nacre. Particularly intriguing are spider silks, with studies having explored properties ranging from their protein sequence to the geometry of a web. This material system, highly adapted to meet a spider's many needs, has superior mechanical properties. In spite of much research into the molecular design underpinning the outstanding performance of silk fibres, and into the mechanical characteristics of web-like structures, it remains unknown how the mechanical characteristics of spider silk contribute to the integrity and performance of a spider web. Here we report web deformation experiments and simulations that identify the nonlinear response of silk threads to stress--involving softening at a yield point and substantial stiffening at large strain until failure--as being crucial to localize load-induced deformation and resulting in mechanically robust spider webs. Control simulations confirmed that a nonlinear stress response results in superior resistance to structural defects in the web compared to linear elastic or elastic-plastic (softening) material behaviour. We also show that under distributed loads, such as those exerted by wind, the stiff behaviour of silk under small deformation, before the yield point, is essential in maintaining the web's structural integrity. The superior performance of silk in webs is therefore not due merely to its exceptional ultimate strength and strain, but arises from the nonlinear response of silk threads to strain and their geometrical arrangement in a web.

Spider silks display generally strong mechanical properties, even if differences between species and within the same species can be observed. While many different types of silks have been tested, the mechanical properties of stalks of silk taken from the egg sac of the cave spider Meta menardi have not yet been analyzed. Meta menardi has recently been chosen as the "European spider of the year 2012", from the European Society of Arachnology. Here we report a study where silk stalks were collected directly from several caves in the north-west of Italy. Field emission scanning electron microscope (FESEM) images showed that stalks are made up of a large number of threads, each of them with diameter of 6.03 ± 0.58 µm. The stalks were strained at the constant rate of 2 mm/min, using a tensile testing machine. The observed maximum stress, strain and toughness modulus, defined as the area under the stress-strain curve, are 0.64 GPa, 751% and 130.7 MJ/m(3), respectively. To the best of our knowledge, such an observed huge elongation has never been reported for egg sac silk stalks and suggests a huge unrolling microscopic mechanism of the macroscopic stalk that, as a continuation of the protective egg sac, is expected to be composed by fibres very densely and randomly packed. The Weibull statistics was used to analyze the results from mechanical testing, and an average value of Weibull modulus (m) is deduced to be in the range of 1.5-1.8 with a Weibull scale parameter (σ(0)) in the range of 0.33-0.41 GPa, showing a high coefficient of correlation (R(2) = 0.97).

Silk is an exceptionally strong, extensible, and tough material made from simple protein building blocks. The molecular structure of dragline spider silk repeat units consists of semiamorphous and nanocrystalline β-sheet protein domains. Here we show by a series of computational experiments how the nanoscale properties of silk repeat units are scaled up to create macroscopic silk fibers with outstanding mechanical properties despite the presence of cavities, tears, and cracks. We demonstrate that the geometric confinement of silk fibrils to diameters of 50 ± 30 nm is critical to facilitate a powerful mechanism by which hundreds of thousands of protein domains synergistically resist deformation and failure to provide enhanced strength, extensibility, and toughness at the macroscale, closely matching experimentally measured mechanical properties. Through this mechanism silk fibers exploit the full potential of the nanoscale building blocks, regardless of the details of microscopic loading conditions and despite the presence of large defects. Experimental results confirm that silk fibers are composed of silk fibril bundles with diameters in the range of 20-150 nm, in agreement with our predicted length scale. Our study reveals a general mechanism to map nanoscale properties to the macroscale and provides a potent design strategy toward novel fiber and bulk nanomaterials through hierarchical structures.

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis. The structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly beta-sheet crystal domains, while disorderly regions are formed by glycine-rich repeats that consist of 3₁-helix type structures and beta-turns. Our structural predictions are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content. Mechanical shearing simulations on selected structures illustrate that the nanoscale behaviour of silk protein assemblies is controlled by the distinctly different secondary structure content and hydrogen bonding in the crystalline and semi-amorphous regions. Both structural and mechanical characterization results show excellent agreement with available experimental evidence. Our findings set the stage for extensive atomistic investigations of silk, which may contribute towards an improved understanding of the source of the strength and toughness of this biological superfibre.

Biological materials such as spider silk display hierarchical structures, from nano to macro, effectively linking nanoscale constituents to larger-scale functional material properties. Here, we develop a model that is capable of determining the strength and toughness of elastic-plastic composites from the properties, percentages, and arrangement of its constituents, and of estimating the corresponding dissipated energy during damage progression, in crack-opening control. Specifically, we adopt a fiber bundle model approach with a hierarchical multiscale self-similar procedure which enables to span various orders of magnitude in size and to explicitly take into account the hierarchical topology of natural materials. Hierarchical architectures and self-consistent energy dissipation mechanisms (including plasticity), both omitted in common fiber bundle models, are fully considered in our model. By considering one of the toughest known materials today as an example application, a synthetic fiber composed of single-walled carbon nanotubes and polyvinyl alcohol gel, we compute strength and specific energy absorption values that are consistent with those experimentally observed. Our calculations are capable of predicting these values solely based on the properties of the constituent materials and knowledge of the structural multiscale topology. Due to the crack-opening control nature of the simulations, it is also possible to derive a critical minimal percentage of plastic component needed to avoid catastrophic behavior of the material. These results suggest that the model is capable of helping in the design of new supertough materials.

Spider dragline silk is one of the strongest, most extensible and toughest biological materials known, exceeding the properties of many engineered materials including steel. Silk features a hierarchical architecture where highly organized, densely H-bonded beta-sheet nanocrystals are arranged within a semiamorphous protein matrix consisting of 3(1)-helices and beta-turn protein structures. By using a bottom-up molecular-based approach, here we develop the first spider silk mesoscale model, bridging the scales from Angstroms to tens to potentially hundreds of nanometers. We demonstrate that the specific nanoscale combination of a crystalline phase and a semiamorphous matrix is crucial to achieve the unique properties of silks. Our results reveal that the superior mechanical properties of spider silk can be explained solely by structural effects, where the geometric confinement of beta-sheet nanocrystals, combined with highly extensible semiamorphous domains, is the key to reach great strength and great toughness, despite the dominance of mechanically inferior chemical interactions such as H-bonding. Our model directly shows that semiamorphous regions govern the silk behavior at small deformation, unraveling first when silk is being stretched and leading to the large extensibility of the material. Conversely, beta-sheet nanocrystals play a significant role in defining the mechanical behavior of silk at large-deformation. In particular, the ultimate tensile strength of silk is controlled by the strength of beta-sheet nanocrystals, which is directly related to their size, where small beta-sheet nanocrystals are crucial to reach outstanding levels of strength and toughness. Our results and mechanistic insight directly explain recent experimental results, where it was shown that a significant change in the strength and toughness of silk can be achieved solely by tuning the size of beta-sheet nanocrystals. Our findings help to unveil the material design strategy that enables silk to achieve superior material performance despite simple and inferior material constituents. This concept could lead to a new materials design paradigm, where enhanced functionality is not achieved using complex building blocks but rather through the utilization of simple repetitive constitutive elements arranged in hierarchical structures from nano to macro.

Silk features exceptional mechanical properties such as high tensile strength and great extensibility, making it one of the toughest materials known. The exceptional strength of silkworm and spider silks, exceeding that of steel, arises from beta-sheet nanocrystals that universally consist of highly conserved poly-(Gly-Ala) and poly-Ala domains. This is counterintuitive because the key molecular interactions in beta-sheet nanocrystals are hydrogen bonds, one of the weakest chemical bonds known. Here we report a series of large-scale molecular dynamics simulations, revealing that beta-sheet nanocrystals confined to a few nanometres achieve higher stiffness, strength and mechanical toughness than larger nanocrystals. We illustrate that through nanoconfinement, a combination of uniform shear deformation that makes most efficient use of hydrogen bonds and the emergence of dissipative molecular stick-slip deformation leads to significantly enhanced mechanical properties. Our findings explain how size effects can be exploited to create bioinspired materials with superior mechanical properties in spite of relying on mechanically inferior, weak hydrogen bonds.