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Posted: Jan 27, 2009
Insight into nature's protein factory could lead to radically new materials design
(Nanowerk Spotlight) In a previous Nanotechnology Spotlight, we describe how, in order to develop tomorrow's supermaterials, scientists need to unlock nature's structural design rules, in particular for nanoscopic hierarchical molecular structures, and make them available to engineers. This is only possible through a deep understanding of the structure-property relations in biological materials. There is also a surprising relationship between these material design issues and the understanding (or rather lack thereof) of genetic diseases, where structural changes are due to mutations on the molecular level that lead to changed chemical and mechanical properties, which in turn lead to a malfunction of the protein network under mechanical load.
Hierarchical nanostructures – ranging through atomistic, molecular and macroscopic scales – represent universal features of biological protein materials. New work by MIT professor Markus Buehler discusses the role of these structural hierarchies in determining properties of biological materials.
This neat model demonstration illustrates how nature combines universality and diversity in order to create optimal structures, making the repeated invention of new building blocks unnecessary when 'designing' novel properties.
"The specific focus of our recent work is the origin of how naturally occurring biological protein materials (e.g. spider silk, bone, tendon, skin) are capable of unifying disparate mechanical properties such as strength (ability to sustain large stresses without fracture) and robustness (ability to undergo deformation without fracture, despite the presence of defects)," Buehler explains to Nanowerk. "The key finding of our study is that by 'simply' changing the way molecules are arranged we can tune the properties of materials and improve their overall performance, without any additional material use. This represents a new paradigm in materials design – not yet explored – that could lead to the development of multi-functional, light-weight materials that combine multiple/disparate properties."
In their paper in Nanotechnology, Buehler and Ackbarow show for the case of alpha-helical protein domains (structures that are found in cells, hair, hoof and many other protein materials) that this use of molecular hierarchies within the structural arrangement leads to an extended physical dimension in the material design space that resolves the conflict between disparate material properties such as strength and robustness – a limitation faced by many synthetic materials.
Buehler points out that optimal combination of redundancies at different hierarchical levels enables superior mechanical performance without additional material use.
The study is facilitated by the development of a model, the Hierarchical Bell Model, which allows the prediction of mechanical properties of hierarchical protein structures. Buehler and Ackbarow validated this model by large-scale molecular dynamics simulations of several model protein structures. Ackbarow notes that the model can predict strength and robustness (i.e. fault tolerance) in dependence of the hierarchical arrangement of individual protein constituents (in this case, alpha-helical elements).
Illustration of different arrangements of alpha-helical protein filaments and their schematic representation in the Hierarchical Bell Model. (Image: Prof. Markus Buehler, MIT)
"Models as reported in our paper are the first step towards the bottom-up engineering design of hierarchical biological and biomimetic materials and nano-structures, existing of single hydrogen bonds (H-bonds) on the lowest hierarchical scale" says Buehler. In nature, these hydrogen bonds are 'weak' bonds (i.e. can be formed at room-temperature), out of which through 'smart' hierarchical arrangements very strong yet robust materials such as spider silk can be built" (see: Protein engineering – from the humble spider to the nanotechnology future of material design).
Up until now, no structure-property link existed for hierarchical protein structures, e.g. those that consist of hierarchically arranged H-bonds, such as alpha-helical protein filaments. The strength could not be directly predicted purely from structural information, and empirical measurements through experiments were necessary.
According to Buehler, the new model allows making predictions of the strength and robustness of such alpha-helix based protein structures, purely from the geometrical information and physical energy parameters, e.g. the rupture energy of a single H-bond.
"Our findings may enable the development of self-assembled de novo bioinspired nanomaterials based on peptide and protein building blocks, and could help in elucidating the mechanistic role of alpha-helical proteins in cell signaling and mechanotransduction" he says. "Our paper gives a specific example of how new peptide nanotubes can be designed".
Potential application include the design of organic and inorganic nanomaterials, such as nanowires, protein networks as well as the development of synthetic tissues for biomedical applications.
While this model is a first step towards designing novel, bioinspired materials, there are numerous challenges to be overcome. "First of all" says Buehler, "we just began understanding these hierarchical protein structures and the basic design rules at the nanoscale. A lot of future work needs to be done in order to get a deeper insight into the behavior of other protein structures, other than alpha-helical proteins as we focused on. Also, additional work at the experimental level must be carried out to further develop validation for the theoretical work."
Although researchers are now able to create nanostructures based on peptides and proteins, they need to achieve a higher degree of controllability of these structures, in particular their self-assembly behavior.
"Finally, once we have understood the design rules and can control associated nanostructures, it is necessary to create macroscopic structures or materials from these nanoelements" Buehler says. "Nature is able to do that, but we are still far away from reaching that goal in the laboratory."
The multi-scale behavior of protein assemblies with the goal of elucidating the relation between structure and material properties represents a grand challenge at the interface of materials science and biology. This gap in understanding could be closed by systematically studying the material properties of hierarchical protein structures, their effect on the macroscopic properties (through development of structure–property relationships), and the role of material properties in their biological context, an effort defined as materiomics.
This research was supported by the National Science Foundation, the Army Research Office, and the Air Force Office of Scientific Research.