Biomedical Engineering Reference
In-Depth Information
peptides after assembly, as well as hydrogel properties such as the solution condi-
tions desired for encapsulated payload release.
There are also hybrid molecules produced through traditional organic or poly-
mer chemistry methods with desired peptide primary sequences attached to poly-
mers, hydrocarbon chains, or even other peptide chains as conjugates. One of the
most common sequences used as a conjugate is the three amino acid sequence of
RGD (arginine, glycine, aspartic acid), used because of its ability to trigger cell
adhesion, a desired feature for cell-hydrogel constructs [
2
,
4
,
6
,
8
,
10
,
36
-
38
].
Because RGD works as an integrin-binding site, there are many variations of
this three amino acid sequence, as well as other integrin-recognized amino acid
sequences, that can be synthesized [
1
,
2
,
6
,
36
,
41
,
43
-
45
]. RGD does not cre-
ate hydrogels itself; rather, RGD is incorporated into other polymer sequences
that go on to create hydrogels through physical assembly or chemical reactions.
While RGD is used biologically to imitate RGD found naturally, there are peptide
sequences that are used for non-natural, non-hydrogel purposes. Taking advantage
of the structure, solution conditions, and availability of peptides, many groups are
using peptide sequences and resultant higher order structure to direct the synthe-
sis, growth and organization of non-peptide, disparate materials, such as graphene,
metallic nanoparticles, or silica dioxide [
76
-
78
].
With the ease of synthesis, there are a vast number of the possible combinations
and permutations of natural and non-natural amino acids with varying sequence
lengths. The length of a peptide sequence affects many of the characteristics of the
hydrogel created. Shorter peptide sequences will generally assemble faster inter-
molecularly with less defective assembly than longer sequences that can coil and
entangle during assembly. Mono- [
20
], di- [
79
,
80
], and tri-peptide [
17
,
26
,
36
,
40
]
sequences that are created as supramolecular gelators tend to be made of amino
acids with naturally hydrophobic or polar but uncharged functional groups [
11
,
34
-
37
,
40
]. Some mono-, di- and tri-peptide sequences retain the Fmoc protec-
tion group at the end of the n-terminus, which is observed to be an integral part
in hydrogel formation with
ˀ
-stacking from the aromatic rings. A change in pH
[
20
,
40
,
42
,
57
,
59
,
61
] to force hydrophobic collapse or the addition of enzymes
[
3
,
16
,
26
,
33
,
47
,
63
] can be used to induce hydrogelation. Figure
1
shows two
di-peptides used in combination to create three different hydrogels and the TEM
images of the fibrils formed [
80
].
When triggered, short amino acid sequences form long fibril networks of pep-
tides to form hydrogels. The peptides generally start as primary structures solu-
ble in solution, but then self assemble intermolecularly into higher order structures
and hydrogels [
1
,
29
,
31
,
33
-
35
,
48
,
50
,
64
,
65
,
81
,
82
]. In order for longer
sequences to self-assemble, longer peptide sequences generally have both hydro-
phobic, uncharged amino acids, while also including hydrophilic and polar groups
to help drive secondary bonding as well as hydrophobic collapse of sequences.
The trigger for longer sequences to intermolecularly assemble into higher order
structures will usually be a change in pH, temperature or ion concentration
although many other stimuli have been designed and will be discussed later in
the chapter. The properties and applications of these higher order structures will
Search WWH ::
Custom Search