The figure above shows the
structure of a beta-sheet protein, Z1-Z2 telethonin complex, in
the giant muscle protein titin. The inset shows the orientation of
the protein backbone of three beta strands (in purple) with
hydrogen bonds (yellow) holding the assembly together. Using
simulation and theory, Buehler and Keten found that hydrogen bonds
in beta-sheet structures break in clusters of three or four, even
presence of many more bonds.
Image � by Sinan Keten and Markus
Based on theoretical modeling and large-scale
atomistic simulation implemented on supercomputers, this new
understanding of exactly how a protein�s configuration enhances a
material�s strength could help engineers create new materials that
mimic spider silk�s lightweight robustness. It could also impact
research on muscle tissue and amyloid fibers found in brain tissue.
�Our hope is that by understanding the mechanics of materials at the
atomistic level, we will be able to one day create a guiding principle
that will direct the synthesis of new materials,� said Professor
Markus Buehler, lead researcher on the work.
In a paper published in the Feb. 13 online issue of Nano Letters,
Buehler and graduate student Sinan Keten describe how they used
atomistic modeling to demonstrate that the clusters of three or four
hydrogen bonds that bind together stacks of short beta strands in a
structural protein rupture simultaneously rather than sequentially
when placed under mechanical stress. This allows the protein to
withstand more force than if its beta strands had only one or two
bonds. Oddly enough, the small clusters also withstand more energy
than longer beta strands with many hydrogen bonds.
�Using only one or two hydrogen bonds in building a protein provides
no or very little mechanical resistance, because the bonds are very
weak and break almost without provocation,� said Buehler, the Esther
and Harold E. Edgerton Assistant Professor in the Department of Civil
and Environmental Engineering. �But using three or four bonds leads to
a resistance that actually exceeds that of many metals. Using more
than four bonds leads to a much-reduced resistance. The strength is
maximized at three or four bonds.�
After observing the simultaneous rupture of these hydrogen-bond
clusters within the proteins in their atomistic simulations, Buehler
and Keten wanted to know why the bonds break in small clusters, even
in long strands with many hydrogen bonds. They used the laws of
thermodynamics to explain this phenomenon. The paper in Nano Letters
describes how the external force changes the entropic energy in the
system and leads to the rupture of hydrogen bonds. By calculating the
energy necessary to initiate the unfolding process in a protein
molecule, they demonstrated that adding more hydrogen bonds in longer
strands would not increase the material�s strength.
�You would simply have this long chain of beta strands with lazy bonds
that don�t contribute to the strength of the assembly,� said Keten.
�But a material that employs many short beta strands folded and
connected by three or four hydrogen bonds may exhibit strength greater
than steel. In metals, the energy would be stored directly in much
stronger bonds, called metallic bonds, until bonds rupture one by one.
In proteins, things are more complicated due to the entropic
elasticity of the noodle-like chains and the cooperative nature of the
Structural proteins contain a preponderance of beta-sheets, sections
that fold in such a way that they look a bit like old-fashioned ribbon
candy; short waves or strands appear to be stacked on top of one
another, each just the right length to allow three or four hydrogen
bonds to connect it to the section above and beneath.
Beta sheets with short strand lengths connected by three or four
hydrogen bonds are the most common conformation among all
beta-structured proteins, including those comprising muscle tissue,
according to experimental proteomics data on protein structures in the
Protein Data Bank.
This correlation of a common geometric configuration among beta sheets
- which are one of the two most prevalent protein structures in
existence - suggests that a protein�s strength
is an important evolutionary driving force behind its physical design.
The researchers observed the same behavior in similar small clusters
in alpha-helical structural proteins, the other most prevalent protein,
but haven�t yet studied those assemblies in detail.
On the other hand, synthetic materials like steel have a very
different and crystalline structure held together by the stronger glue
of metallic bonds. Because steel and other synthetic materials tend to
be dense, and therefore heavy, they consume a good deal of energy in
manufacturing and transport.
�Metals are configured with bonds that are much stronger and require a
much greater force to break,� said Buehler. �However, the crystalline
lattice of a metal�s structure is never perfect; it contains defects
that effectively reduce the material�s strength quite drastically.
When you place a load on the metal, the defect can fail, possibly
causing a crack to propagate. In protein�s beta sheets, the confined
nature of the hydrogen bond clusters helps to dissipate the energy
without compromising the strength of the material. This shows the
amazing ingenuity and efficiency of natural materials.�
This research was supported by an MIT Presidential Graduate Fellowship,
the Army Research Office, a National Science Foundation CAREER Award,
the Solomon Buchsbaum AT&T Research Fund, and a grant from the San
Diego Supercomputing Center (SDSC).