Biomedical Engineering Reference
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The scaffolds consist of alternating amino acids that contain 50% charged residues
(Zhang et al. 1993, 1994, 1995 ; Holmes et al. 2000 ; Caplan et al. 2002 ; Kisiday
et al. 2002 ; Gelain et al. 2006 ; Horii et al. 2007 ; reviewed by Gelain et al. 2007a, b ) .
These peptides are characterized by their periodic repeats of alternating ionic hydro-
philic and hydrophobic amino acids with a typical b-sheet structure. Thus, these
b-sheet peptides have distinct polar and non-polar surfaces. The self-assembly event
creating the peptide scaffold takes place under physiological conditions. They are
like gel-sponge in aqueous solution and readily transportable to different environ-
ments. Individual fi bers are ~10 nm in diameter. A number of additional self-assembling
peptides including RADA16-I (AcN-RADARADARADARADA-CNH2) (shown
in Fig. 3b ) and RADA16-II (AcN-RARADADARARADADA-CNH2), in which
arginine and aspartate residues substitute lysine and glutamate, have been designed
and characterized for salt-facilitated nanofi ber scaffold formation. The alanines
form overlap packed hydrophobic interactions in water, a structure that is found in
silk fi broin from silkworm and spiders. On the charged sides, both positive and
negative charges are packed together through intermolecular ionic interactions in a
checkerboard-like manner. In general, these self-assembling peptides form stable
b-sheet structures in water, which are stable across a broad range of temperature,
wide pH ranges in high concentration of denaturing agent urea and guanidium
hydrochloride. The nanofi ber density correlates with the concentration of peptide
solution and the nanofi ber retains extremely high hydration, >99% in water
(5-10 mg/ml, w/v) (Fig. 4 ).
The peptide synthesis method uses conventional mature solid phase peptide syn-
thesis chemistry. Depending on the length of the motifs, high purity of peptides can
be produced at a reasonable cost. Since cost of the peptide synthesis has decreased
steadily in last few years, it has become more and more affordable.
Many self-assembling peptides that form scaffolds have been reported and the
numbers are still expanding (Zhang and Altman 1999 ; Zhang 2002 ) . The formation
of the scaffold and its mechanical properties are infl uenced by several factors, one
of which is the level of hydrophobicity (Marini et al. 2002 ; Caplan et al. 2002 ). That
is, in addition to the ionic complementary interactions, the extent of the hydropho-
bic amino acids, Ala, Val, Met, Ile, Leu, Tyr, Phe, Trp (or single letter code, A, V,
M, I, L, Y, P, W) can signifi cantly infl uence the mechanical properties of the scaf-
folds and the speed of their self-assembly. The higher the content of hydrophobicity,
the easier it is for scaffold formation and the better for their mechanical properties
(Marini et al. 2002 ; Caplan et al. 2002 ; Kisiday et al. 2002 ) .
The Molecular Lego Peptides
Molecular-designed “Lego Peptide”, at the nanometer scale, resembles the Lego
bricks that have both pegs and holes in a precisely determined manner and can be
programmed to assemble in well-formed structures. This class of “Lego peptide”
can spontaneously assemble into well-formed nanofi bers (Zhang et al. 1993 ) . The
fi rst member of the Lego peptide was EAK16-II mentioned above and serendipitously
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