Matriarch: A Python Library for Materials Architecture

Biological materials, such as proteins, often have a hierarchical structure ranging from basic building blocks at the nanoscale (e.g., amino acids) to assembled structures at the macroscale (e.g., fibers). Current software for materials engineering allows the user to specify polypeptide chains and simple secondary structures prior to molecular dynamics simulation, but is not flexible in terms of the geometric arrangement of unequilibrated structures. Given some knowledge of a larger-scale structure, instructing the software to create it can be very difficult and time-intensive. To this end, the present paper reports a mathematical language, using category theory, to describe the architecture of a material, i.e., its set of building blocks and instructions for combining them. While this framework applies to any hierarchical material, here we concentrate on proteins. We implement this mathematical language as an open-source Python library called Matriarch. It is a domain-specific language that gives the user the ability to create almost arbitrary structures with arbitrary amino acid sequences and, from them, generate Protein Data Bank (PDB) files. In this way, Matriarch is more powerful than commercial software now available. Matriarch can be used in tandem with molecular dynamics simulations and helps engineers design and modify biologically inspired materials based on their desired functionality. As a case study, we use our software to alter both building blocks and building instructions for tropocollagen, and determine their effect on its structure and mechanical properties.Center for Excellence in Education. Research Science InstituteUnited States. Office of Naval Research. Presidential Early Career Award for Scientists and Engineers (N000141010562)United States. Air Force. Office of Scientific Research (FA9550-11-1-0199)United States. Army Research OfficeNational Institutes of Health (U.S.) (5U01EB016422)National Institutes of Health (U.S.) (EB014976)BASF. North American Center for Research on Advanced Material

Secondary Structure Transition and Critical Stress for a Model of Spider Silk Assembly

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 N. 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 identified the smallest molecule size that gives rise to a 'silk-like' structure contains six poly-alanine 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 poly-alanine section these amino acids include glycine, leucine and glutamine. 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

Aqueous peptide-TiO2 interfaces: iso-energetic binding via either entropically- or enthalpically-driven mechanisms

A major barrier to the systematic improvement of biomimetic peptide-mediated strategies for the controlled growth of inorganic nanomaterials in environmentally benign conditions lies in the lack of clear conceptual connections between the sequence of the peptide and its surface binding affinity, with binding being facilitated by non-covalent interactions. Peptide conformation, both in the adsorbed and non-adsorbed state, is the key relationship that connects peptide-materials binding with peptide sequence. Here, we combine experimental peptide–titania binding characterization with state-of-the-art conformational sampling via molecular simulations to elucidate these structure/binding relationships for two very different titania-binding peptide sequences. The two sequences (Ti-1: QPYLFATDSLIK and Ti-2: GHTHYHAVRTQT) differ in their overall hydropathy, yet via quartz-crystal microbalance measurements and predictions from molecular simulations, we show these sequences both support very similar, strong titania-binding affinities. Our molecular simulations reveal that the two sequences exhibit profoundly different modes of surface binding, with Ti-1 acting as an entropically-driven binder while Ti-2 behaves as an enthalpically-driven binder. The integrated approach presented here provides a rational basis for peptide sequence engineering to achieve the in-situ growth and organization of titania nanostructures in aqueous media and for the design of sequences suitable for a range of technological applications that involve the interface between titania and biomolecules

The nature of the silicaphilic fluorescence of PDMPO

PDMPO (2-(4-pyridyl)-5-((4-(2-dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole), has unique silica specific fluorescence and is used in biology to understand biosilicification. This ‘silicaphilic’ fluorescence is not well understood nor is the response to local environmental variables like solvent and pH. We investigated PDMPO in a range of environments: using UV-vis and fluorescence spectroscopy supported by computational data, (SPARC, molecular dynamics simulations, density functional theory calculations), dynamic light scattering and zeta potential measurements to understand the PDMPO–silica interaction. From absorption data, PDMPO exhibited a pKa of 4.20 for PDMPOH22+ to PDMPOH+ . Fluorescence emission measurements revealed large shifts in excited state pKa* values with different behaviour when bound to silica (pKa* of 10.4). PDMPO bound to silica particles is located in the Stern layer with the dye exhibiting pH dependent depolarising motion. In aqueous solution, PDMPO showed strong chromaticity with correlation between the maximum emission wavelength for PDMPOH+* and dielectric constant (4.8–80). Additional chromatic effects were attributed to changes in solvent accessible surface area. Chromatic effects were also observed for silica bound dye which allow its use as a direct probe of bulk pH over a range far in excess of what is possible for the dye alone (3–5.2). The unique combination of chromaticity and excited state dynamics allows PDMPO to monitor pH from 3 to 13 while also reporting on surface environment opening a new frontier in the quantitative understanding of (bio)silicification

Category Theoretic Analysis of Hierarchical Protein Materials and Social Networks

Materials in biology span all the scales from Angstroms to meters and typically consist of complex hierarchical assemblies of simple building blocks. Here we describe an application of category theory to describe structural and resulting functional properties of biological protein materials by developing so-called ologs. An olog is like a “concept web” or “semantic network” except that it follows a rigorous mathematical formulation based on category theory. This key difference ensures that an olog is unambiguous, highly adaptable to evolution and change, and suitable for sharing concepts with other olog. We consider simple cases of beta-helical and amyloid-like protein filaments subjected to axial extension and develop an olog representation of their structural and resulting mechanical properties. We also construct a representation of a social network in which people send text-messages to their nearest neighbors and act as a team to perform a task. We show that the olog for the protein and the olog for the social network feature identical category-theoretic representations, and we proceed to precisely explicate the analogy or isomorphism between them. The examples presented here demonstrate that the intrinsic nature of a complex system, which in particular includes a precise relationship between structure and function at different hierarchical levels, can be effectively represented by an olog. This, in turn, allows for comparative studies between disparate materials or fields of application, and results in novel approaches to derive functionality in the design of de novo hierarchical systems. We discuss opportunities and challenges associated with the description of complex biological materials by using ologs as a powerful tool for analysis and design in the context of materiomics, and we present the potential impact of this approach for engineering, life sciences, and medicine.Presidential Early Career Award for Scientists and Engineers (N000141010562)United States. Army Research Office. Multidisciplinary University Research Initiative (W911NF0910541)United States. Office of Naval Research (grant N000141010841)Massachusetts Institute of Technology. Dept. of MathematicsStudienstiftung des deutschen VolkesClark BarwickJacob Luri

Structural heterogeneity in silk fibers and its effects on failure mechanics and supercontraction

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Civil and Environmental Engineering, 2015.Cataloged from PDF version of thesis.Includes bibliographical references (pages 177-196).Spider dragline silk is a protein material that has evolved over millions of years to become one of the strongest and toughest natural fibers known. Silk features a heterogeneous structure that comprises [beta]-sheet crystals embedded in an amorphous matrix. However, it is not fully understood how the heterogeneity of silk affects its mechanical properties. First, the origin of the nanoscale heterogeneity during the Nephila Clavipes dragline silk assembly is investigated. Using molecular dynamics simulations, a shear flow at natural pulling speeds is modelled and the secondary structure transitions as well as shear stresses in the silk protein chains are determined. It is shown that under shear stresses beyond the elastic regime, silk undergoes an [alpha] -- [beta] transition in the spinning duct. The stability of the assembled [beta]-sheet structure seems to arise from a close proximity of the [alpha]-helices in the silk solution. The smallest molecule size that might give rise to a silk-like structure is determined to comprise four to six repeats of the silk sequence. Establishing the molecular details of the assembly can guide the design of microfluidic devices and the synthesis of bioinspired protein materials. Second, it is shown how the heterogeneity of silk fibers, specifically its crystalline phase, relates to its fracture mechanical properties: strength and toughness. Analytical fracture mechanical arguments are presented to illustrate the relation between fracture strength and heterogeneity in silk and other biopolymers. Nanoconfinement and flaw tolerance are presented as natural strategies to increase the mechanical performance of the entire material system. It is shown that the consideration of interatomic interactions alone cannot explain the fracture strength observed in biological fibers. Instead, structures at multiple length-scales must be considered to explain the remarkable mechanical performance and resilience of silk. Third, the interaction of water with silk's heterogeneous nanostructure is investigated. At high humidity, some spider dragline silks will shrink up to 50%, a phenomenon known as supercontraction. The molecular origin of dragline silk supercontraction is explored using a full-atomistic model and molecular dynamics supported by in situ Raman spectroscopy and mechanical testing performed at the Max Planck Institute in Potsdam, Germany. Tyrosine and Arginine are identified as the key residues in the Nephila Clavipes silk sequence that control supercontraction. A genetic engineering strategy to alter silk's behavior to industrial requirements is proposed, where sequence mutations reduce or even reverse the supercontraction mechanism.by Tristan Giesa.Ph. D

Nanoconfinement of Spider Silk Fibrils Begets Superior Strength, Extensibility, and Toughness

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.United States. Army Research Office. Multidisciplinary University Research Initiative (Award 991NF-09-1-0541)United States. Office of Naval Research (Presidential Early Career Awards for Scientists and Engineers Award N000141010562