Chemistry Reference
In-Depth Information
coiled coil dimer. Although important questions can still be raised at this point as to
how to control the size of the higher ordered structure, the work presented here defi-
nitely proves the feasibility of utilizing de novo designed helical peptides to mimic
their natural counterparts. At the same time, it encourages further exploration to
seek for more building blocks with diverse molecular and structural information
that can be delivered to the resultant self-assemblies. To this end, the same group syn-
thesized several types of nonlinear peptides that are able to coassemble with the orig-
inally designed SAF peptides during fibrillogenesis (Ryadnov and Woolfson 2003a,
2003b, 2005). The fiber or fiber network morphology largely depends on the struc-
tural feature presented by the coassembled peptides, leading to nanofibers with dis-
tinct structural morphology (kinks, twists, branches, segments, polygonal networks).
In addition to morphology control, efforts have also been made to understand the
self-assembly in terms of the longitudinal elongation induced by the head-tail
packing and lateral aggregation facilitated by the side-by-side packing between
fibrils. Rodamine-labeled SAF-p2a (mutant of SAF-p2) was mixed with the
preformed fibers composed of SAF-p1 and SAF-p2a. It was found that fluorescent-
labeled peptide was only attached on one end of the preformed fibers. This result
indicated a unidirectional fiber growth directed by the inherent polarity of the SAF
peptides with opposite charge domains dominating N- and C-termini (Smith et al.
2005). The issue of lateral aggregation occurring during fibrillogenesis is a very
common phenomenon for natural protein fibers having a repeated pattern with
complemented structural features. Considering the highly structural similarity and
complementarities within the coiled coil building blocks, it would not be surprising
to see the higher ordered packing taking place during self-assembly and fiber for-
mation. Although the complete answer to these questions still awaits more detailed
kinetics and molecular structural studies with a variety of spectroscopy methods,
two papers published recently by Woolfson's group (Smith et al. 2006;
Papapostolou et al. 2007) shed light on the understanding of the molecular and nanos-
tructrual organization within coiled coil fiber bundles and should help the design of
coiled coil based nanofibrous materials with engineered nanoscale order and stability.
Considering the important role electrostatic interaction plays in the formation and
stabilization of self-assembly, redesigned peptides were incorporated with additional
ion pairs of Arg-Asp to strength the charge interaction. Collected data from circular
dichroism (CD) and TEM all suggests increased stability compared to that of the first
generation. It is worth noting that the second generation yielded fibers with higher salt
tolerance, a significant improvement if these materials are to be considered in cell
culture or other applications requiring physiological salt levels.
The most recent generation of peptides modified from the original SAF-1 and
SAF-2 created a striation pattern across the entire length of nanofibers upon self-
assembly, revealing a remarkable control on the nanoscale level within each fiber
bundle. A molecular model was proposed and supported by the data obtained by
TEM and X-ray diffraction analysis, indicating the coiled coil dimer self-assembled
into a 3-D hexagonally packed lattice with a size of 1.8 nm and a periodicity of
4.2 nm along the fiber axis. The fact that the specific pattern of striation is reminiscent
of what has been observed in natural collagen holds great promise in the development
