Biomedical Engineering Reference
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Fig. 5 Three distinct types of self-assembling “Lego peptides.” These peptides have two sides,
one hydrophobic ( green ) and another hydrophilic ( red and blue )
Fig. 6 The designer lipid-like peptides. They have either negatively charged head ( red ) or posi-
tively charged head ( blue ) or mixed charged head ( half red and half blue in both sites). The tails
can be any hydrophobic amino acids ( green )
discovered from Zuotin (zuo means left in Chinese, while tin is suffi x to assign its
peptide nature) (Zhang et al. 1992 ).
The Lego peptide molecules can undergo self-assembly in aqueous solutions to
form well-ordered nanofi bers that further associate to form nanofi ber scaffolds
(Fig. 4 ). One of them, RADA16-I, is widely used as a designed biological scaffold
in contrast to other biologically derived scaffolds from animal collagen and Matrigel,
which contain unspecifi ed components in addition to known materials (Fig. 3 ).
Lego peptides can form stable b-strand and b-sheet structures, thus the side
chains partition into two sides, one polar and the other nonpolar (Fig. 5 ). They
undergo self-assembly to form nanofi bers with the nonpolar residues inside (green)
and positively (blue) and negatively (red) charged residues form complementary
ionic interactions, like a checkerboard.
Since these nanofi ber scaffolds contain 5-200 nm pores and have extremely high
water content (>99.5% or 1-5 mg/ml), they have been used as 3-D cell-culture
media. The scaffolds closely mimic the porosity and gross structure of extracellular
matrices, allowing cells to reside and migrate in a 3-D environment and molecules,
such as growth factors and nutrients, to diffuse in and out very slowly. These peptide
scaffolds have been used for 3-D cell culture, controlled cell differentiation, tissue
engineering and regenerative medicine applications.
4.1.3
Designer Lipid-Like Peptides
The second class of the self-assembling peptide belongs to a lipid-like molecule.
These peptides have a hydrophilic head and a hydrophobic tail, much like lipids or
detergents. They sequester their hydrophobic tail inside of micelle, vesicles or nano-
tube structures and their hydrophilic heads expose to water. At least four kinds of
molecules can be made, with negative, positive, zwitterionic (±, mixed charge)
heads (Vauthey et al. 2002 ; Santoso et al. 2002 ; von Maltzahn et al. 2003 ) (Fig. 6 ).
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