Controlling peptide-

based hydrogelation
Hydrogels can be formed by the self-assembly of certain small molecules.
Many of these hydrogelating molecules assemble under specific conditions
into nanofibers. The entanglement of these fibers leads to the matrix of the
gel. Preparing gels with reproducible properties requires careful control
of the self-assembly. Here, we describe recent methods for controlling the
assembly of a range of oligopeptide-based gelators, using triggers such as
pH, salts, and in situ reduction. We focus on the different methods available
to trigger gel formation, rather than attempting to describe all examples
of each. The oligopeptide gelators have applications in areas including cell
culturing, controlled release, catalysis and energy materials.

Huaimin Wang1, Zhimou Yang1,*, and Dave J. Adams2,*

1.
State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, P. R. China
2.
Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, U.K.
*E-mail: yangzm@nankai.edu.cn; d.j.adams@liverpool.ac.uk

Molecular hydrogels are formed by the self-assembly of small molecules
such as peptides or derivatives of sugars1, 2, base pairs3, 4, and amino acids5, 6.
These gels have great potential in tissue engineering7-9, controlled drug
delivery10-18, and regenerative medicine19-22 due to their biocompatibility,
high water content, and degradability. Molecular hydrogels have also
been applied as templates for mineralization of organic and inorganic
materials23-27, as matrices for drug delivery9-17, and as platforms for
screening of bioactive molecules28, 29. Gel formation occurs when these
low molecular weight gelators (LMWG) self-assemble into fibrous
structures. The entanglement of these fibers leads to the matrix of
the gel (Fig. 1). In order to form a molecular hydrogel, an external
stimulus is usually needed. For example, molecular hydrogels can be
formed by using a heating-cooling cycle;30 heating a suspension of a
suitable hydrogelator leads to a homogeneous solution and then a gel
will form after cooling back to room temperature. Many methods have
been developed to form molecular hydrogels using stimuli including
pH31, 32 and ionic strength adjustments33, sonication34,35, organic solvent
assistance36-39, and light-irradiation2, 40, 41.
For applications of gels, the mechanical properties of the gels are often
critical. For example, in cell culturing applications, the mechanical
properties of the supporting gel can affect a number of cell types and
impact the properties of cultured cells.42 In drug delivery, injectable gels
are often desirable and so the ability of the gels to re-heal after shearing
is important43. Hence, understanding how to control the mechanical
properties is of paramount importance.
Intuitively, the mechanical properties of gels prepared using LMWG will
be affected by both the choice of LMWG and the method by which the gels
are prepared. There are many different LMWG known;44-47 different LMWG
gel water at different concentrations, temperatures, etc. It is also worth
noting at this point that specific design rules for LMWG are still unclear.
Additionally, for a specific LMWG, the method of assembly, and hence gel
formation, will affect key factors including the rate of fiber assembly, degree

500 NOVEMBER 2012 | VOLUME 15 | NUMBER 11 ISSN:1369 7021 © Elsevier Ltd 2012 . Open access under CC BY-NC-ND license.
 Controlling peptide- based hydrogelation
of entanglement and spatial arrangement of the fibers46. All these factors
will determine the mechanical properties. The mechanical properties of
the gels arise from the structures at three different length scales: (1) the
average thickness and mechanical properties of the fibers themselves, (2)
the degree of branching (i.e., the distance between the cross-linking points)
and (3) the microstructure (i.e., how the fibers are distributed at a larger
length scale). These parameters are governed by the assembly process46.
For example, we have shown that gels can be formed from FmocLG (in this
review, we will use one letter codes for the amino acids), a functionalized
dipeptide by adding water to a solution of FmocLG in DMSO48. The gels
have significantly different properties depending on the ratio of DMSO:
water (φDMSO). At φDMSO = 0.10, the gels re-heal well after shear. At
φDMSO = 0.30, they recover badly. TEM and SANS showed that the fibers
formed at both these φDMSO were very similar. Instead, the recovery after
shear could be linked to the microstructure (Fig. 2). At φDMSO = 0.10, the
fibers are dispersed in spherulitic domains; at φDMSO = 0.30, the fibers
are dispersed in a homogeneous network. Microstructure in LMWG gels
can also be controlled by using additives.
Here, we review some of the recent developments in methods for the
preparation of hydrogels via the self-assembly of peptide-based LMWG.
Homogeneous molecular hydrogels exhibit promising properties for the
encapsulation of cells, preparation of hybrid hydrogel systems, regenerative
medicine, etc. Among these methods, enzymatic hydrogelation is probably
the most extensively investigated and there are several review papers about
molecular hydrogels prepared by this method49, 50.
Methods to prepare homogeneous molecular
hydrogels
Controlled pH adjustment
A number of peptide-based LMWG can form gels when a solution at
high pH is acidified. For example, Xu showed in 2003 that FmocAA could
form gels at pH 351. Later, Ulijn’s group demonstrated that a number of
other Fmoc-dipeptides also formed gels in this way,8 including FmocFF,
which is a rare example that forms gels at physiological pH52. Many of
these Fmoc-dipeptides are extremely hydrophobic and we found that the
mixing of mineral acids to lower the pH tended to occur on a timescale
that was slower than the gelation.32 Mixing was therefore an issue and
tended to result in gels with irreproducible material properties. Further
work later discussed this in more detail53, 54.
To get around this issue with mixing, we introduced the use of glucono-
δ-lactone (GdL) as a means of adjusting the pH of a solution32. GdL is very
water-soluble and hydrolyses in water to gluconic acid54. Crucially, the rate
of dissolution is higher than the rate of hydrolysis. As a result, uniform
mixing occurs and hence a uniform pH change. This has the immediate
benefit of providing very reproducible gels. Fig. 3 shows gels formed from
the same stock solution adjusted to the same final pH with either HCl
or GdL. The obvious improvement in homogeneity observed in the GdL
sample directly translated into improved mechanical properties of the gel
(storage modulus, G′ = 184 kPa as compared to G′= 5 kPa when using HCl
to adjust the pH). Another benefit is that the timescale for hydrolysis is
suitably slow that it is possible to use this method to observe the assembly
process.32, 56 We have used this specifically to monitor the self-assembly
using techniques such as circular dichroism, IR, TEM and fluorescence56.
REVIEW
Fig. 1 Schematic showing assembly of LMWG into fibers. These entangle and form
the matrix, resulting in a self-supporting hydrogel.
(a) (b) (c)
Fig. 2 Confocal micrographs for FmocLG gels formed at (a) φDMSO = 0.10; (b)
φDMSO = 0.30. The scale bars represent 10 μm. (c) Recovery of G′ after subjecting
the gels to high strain.47
Using GdL, it is possible to target a specific final pH. Alternatively, it is
possible to target a lower final pH, so passing through higher pH values
on route to this lower pH. Hence, this GdL method can be really useful
to try and deconvolute the importance of kinetics and absolute pH value
in these systems.
Other recent routes to adjusting the pH in induce hydrogelation have
included the use of photoacid generators (PAG)57. Here, on exposure to UV
light, a PAG releases protons. We recently demonstrated that this could
be used to trigger gelation in a number of dipeptide-based systems. As
for other pH-triggered routes, fibrillar networks were formed, leading to
invertable gels. Using a PAG to adjust the pH has the advantage that the
gelation can be localized. When part of a sample was masked, gelation
only occurred in the region exposed to the UV light (Fig. 4). This opens
up the possibility of using such materials in the future to make patterned
channels of gels for use in microfluidics and for use in biosensors.
Other examples of adjusting the pH to bring about gelation include the
use of glucose in the presence of an enzyme, glucose oxidase. The enzyme
converts the glucose to gluconic acid, resulting in a pH change as for the
hydrolysis of GdL58. Binding of a sugar to a boronic acid can also induce
a drop in pH. Recently, Grigoriou et al. showed that this binding could be
used to induce gelation in dipeptide-based systems59. Gels formed in the
presence of fructose, but not glucose since glucose has a weaker binding
constant to boronic acids.
Metal ion trigger
Zinc-triggered hydrogelation of a self-assembling
β-hairpin peptide
Schneider and Pochan have conducted pioneering work in developing
β-hairpin peptide hydrogels15, 60-64. The self-assembly and hydrogelation of
β-hairpin peptides are usually triggered by ionic strength enhancement60
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REVIEW Controlling peptide- based hydrogelation
Fig. 3 Photographs of hydrogels prepared from FmocLG. (Left) pH adjusted using
HCl; (Right) pH adjusted using GdL. In both cases, the final pH is 3.9.32
Fig. 4 Stages of gel formation in the presence of UV mask. From top left to right –
Solution of dipeptide-gelator and PAG before UV irradiation; after UV irradiation;
removal of mask shows only gelation of the exposed region occurs; after excess
liquid removed – slight syneresis of gel57.
and the resulting hydrogels can be applied for controlled release of
therapeutic agents15, 16, 3D cell culture65, 66, and tissue engineering67. Recently,
a novel method to initiate peptide self-assembly and hydrogelation was
reported based on the addition of metal ions68. Metal ions have been
used in many instances for tuning gelation in a range of systems69-72.
Micklitsch et al. incorporated a non-natural metal-binding amino acid,
3-amidoethoxyaminodiacetoxy-2-aminopropionic acid (Fig. 5c), into
the peptide to produce a zinc-binding heparin peptide (ZnBHP, Fig. 5).
ZnBHP was unfolded and soluble in aqueous solutions in the absence
502 NOVEMBER 2012 | VOLUME 15 | NUMBER 11
of zinc ions. The addition of zinc ions initiated the self-assembly of the
peptide and led to hydrogelation. The binding was very specific for zinc.
The amount of zinc present in the hydrogel network could be controlled
by the amount of self-assembling peptide used to form the hydrogel.
Topical administration of zinc can enhance healing of both acute and
chronic wounds, as well as inhibit bacterial infection. Hence, hydrogels
with a controllable concentration of zinc ions could be an ideal biomaterial
for wound healing.
A similar strategy was also used to initiate peptide self-assembly via
the binding of heavy metal ions such as Zn2+, Hg2+, Cd2+, and Pb2+.73 A
gelation system based on heavy metal ions binding could find potential
use in heavy metal ion detection via its easily observed sol–gel phase
transition. Here, the sequence VKVKVKV-KVDPPTK- VKVKVKV-NH2 of
the basic self-assembling peptide was modified to VKVKVKVC-CGPKEC-
VKVKVKV-NH2. The thiol groups on the cysteines can bind to metal ions,
promoting hairpin formation. This metal-binding peptide formed gels in
the presence of several heavy metal ions. Interestingly, circular dichroism
studies demonstrated that the rate of β–sheet formation was largely
independent of the identity of the metal ion. However, the rheological
data demonstrated that the rate of network formation for the peptide
is metal-dependent. This implies that the metal ions participate in the
network, for example by crosslinking fibrils in the network via chelation.
As a result, the stiffness of the gels was found to be metal dependent.
Calcium ions to cross-link supramolecular
nanofibers for hydrogelation
Calcium ions have a strong affinity to molecules bearing multiple
carboxylic acid groups or phosphoric acid group at neutral or high pH values.
Therefore, calcium ions can be used to cross-link self-assembled nanofibers of
peptides which incorporate such chemical groups, resulting in the formation of
hydrogels. The research group of Stupp has pioneered the use of calcium ions
to cross-link self-assembled nanofibers of peptide-amphiphiles (oligopeptides
bearing alkyl chains at the N-terminus of the peptide) bearing phosphoric
acid groups and have successfully tailored the mechanical properties of
the resulting hydrogels by control of peptide structure74, 75. Stimulated by
these results, Shi et al. designed a self-assembling functionalized peptide
(N’FGLDD, Fig. 6a) with multiple carboxylic acid groups76. N’FGLDD could
not form hydrogels at neutral pH. Upon the addition of calcium ions
however, N’FGLDD self-assembled into nanofibers and hence produced a
hydrogel. The mechanical properties of resulting gels could be tailored with
the concentration of calcium ions added. For example, when the ratio of
[Ca2+]/[COOH] was increased from 0.13 to 0.77, the storage modulus (G′)
increased from 1.3 Pa to 1.6 × 105 Pa.
Recently, we have demonstrated that the addition of divalent cations
to a solution of a naphthalene-dipeptide at high pH values could lead to
hydrogelation.77 Specifically, certain naphthalene-dipeptides form viscous
solutions due to the presence of worm-like micelles at pH values above the
apparent pKa of the terminal carboxylic acid (Fig. 7). The addition of CaCl2
results in cross-links between these worm-like micelles and hence hydrogel
formation (Fig. 7b). Since these naphthalene-dipeptides can also form gels
at low pH values (below the pKa of the carboxylic acid),78 a gel-to-sol-to-gel
phase transition could be achieved by addition of GdL on the top of salt-
induced gel at high pH values. The hydrolysis of GdL to gluconic acid (see
 Controlling peptide- based hydrogelation REVIEW

(a)

(b) (c)

Fig. 5 (a) Mechanism of metal-triggered folding and self-assembly of ZnBHP. (b) Primary sequences of ZnBHP and control peptide. (c) Structure of 1
(3-amidoethoxyaminodiacetoxy- 2-aminopropionic acid). Reproduced from68 with permission from John Wiley and Sons.

Fig. 6 N’FGLDD self-assembles in the presence of calcium to form nanofibers. This leads to gel formation. The storage modulus (G′) of the gels depends on the ratio
[CaCl2]/[COOH]. Reprinted with permission from76. Copyright 2011 American Chemical Society.

above) results in a decrease in the pH value of the salt-induced gel, leading to
the transition from salt-induced gel to pH-induced gel. This approach could
also be used to prepare interesting single-gelator system with dramatic pH
gradients (Fig. 7c). These results and those from the Xu group where calcium
ions induce gelation (see above) expand the range of short-peptide based
hydrogelators that can be used at physiological pH values.
Related to this work, Roy et al. have recently shown that Fmoc-YL formed
gels at pH 8 in the presence of salts at concentrations of 100 mM79. The
effect of the salts was linked to the Hofmeister series, with the kosmotropes
(water-structuring salts) leading to stiffer gels as compared to the chaotropes
(water-structure breakers).
Supramolecular hydrogels based on the
epitope of potassium ion channels
In the potassium channel, four parallel K+ binding epitopes (TIGYGs)
form a K+ filter that allows the selective flow of K+ ions80. Xu designed a new
gelator on this binding epitope, synthesizing Fmoc-TIGYG (Fig. 8)81. Fmoc-
TIGYG was shown to self-assemble into nanofibers with multiple epitopes
that could mimic the potassium ion channel. Using KOH to adjust the pH
value, nanofibers were formed with widths of about 11 nm in the presence
of K+ ([Fmoc-TIGYG] = 0.05 wt%; ratio of [K+]/[Fmoc-TIGYG] = 2.33).
However, Fmoc-TIGYG did not form a gel but rather a solution at a pH of
4.9, probably due to the lack of sufficient cross-linking points. When the
ratio of [K+]/[Fmoc-TIGYG] was increased to 12.33, the solution changed
to a gel as K+ bound to TIGYG from different fibers, generating cross-links.
Upon a further increase of the K+ concentration, the fibers became thinner,
resulting in weaker gels. In comparison, Fmoc-TGGIY, which does not have
the potassium ion channel epitope, could not form gels in the presence of
K+. These results show that self-assembly generates epitope repeats. These
can interact with specific targets when multiple epitopes are necessary
(i.e. self-assembled multivalency).
Disulfide reduction
A reductive trigger for peptide self-assembly and
hydrogelation
Recently, Nilsson’s group designed a reductive strategy for peptide
self-assembly and subsequent hydrogelation82. As shown in Fig. 9, a short
self-assembling peptide sequence with cysteine (C) residues was designed.
The advantage of this design is that the sulfydryl group at the flank of the
peptide enables macrocyclization of these peptides, preventing β-sheet
formation and self-assembly whilst in the cyclic form. This constraint
could be removed by simple reduction of the disulfide bond, resulting
in relaxation to the stable β-strand and thus triggering self-assembly
of the resulting linear peptide (Fig. 8). Suitable reductants included
tris(2-carboxyethyl)phosphine (TCEP) or dithiothreitol (DTT). This strategy
could be generally applicable to many short self-assembling peptide
sequences. Reducing and oxidizing conditions are important in biologically-
relevant microenvironments. Hence, this methodology could be used to
carry out stimulus-responsive self-assembly in biomaterials and biomedical
applications.

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REVIEW Controlling peptide- based hydrogelation

(a) (b)

(c)

Fig. 7 (a) The hydrogelator assembles into worm-like micelles above the pKa of the terminal carboxylic acid. (b) Schematic of worm-like micelles cross-linked on addition
of a divalent ion (blue). (c) Ca-induced gel at pH 11.7 formed on top of pH-induced gel of hydrogelator at pH 3.4. Both gels contain Universal Indicator. Over time, the
pH equilibrates.

Fig. 8 Schematic of the morphological changes in the nanofiber network with increasing [K+]. Reproduced from81 with permission of The Royal Society of Chemistry.

Fig. 9 Cyclic to linear peptide conformational switch using a reductive trigger. Reprinted with permission from82. Copyright (2010) American Chemical Society.

Disulfide bond as a cleavable linker for
molecular self-assembly and hydrogelation
Stimulated by the development of the reductive strategy to trigger
hydrogelation (see previous section), the Yang group designed a disulfide
linker to connect a molecular hydrogelator to a solubilising hydrophilic
group83. NapGFFY (Fig. 10) was chosen as an effective hydrogelator, with
the penta-peptide EERGD acting as the hydrophilic fragment. The disulfide
bond of the precursor (Fig. 10) could be cleaved by the addition of reductants
such as DTT, TCEP, and glutathione (GSH). On reduction, the molecular
hydrogelator Nap-GFFYE-s was released, which self-assembled, giving a
self-supporting hydrogel. This design concept using the disulfide linker
could also be used to connect other hydrophobic gelators including drugs.
Since GSH is a biocompatible component in living systems, this efficient
method of using GSH to trigger gelation will provide a biocompatible way
to prepare homogeneous hydrogels for cells encapsulation and cell delivery.
This method has been used to prepare several hydrogelating systems based
on taxol derivatives that have potential for chemotherapy84-86.
Other methods
Molecular hydrogelation assisted by protein-peptide
specific interactions
Specific protein-peptide interactions have been used for the formation
of polymeric hydrogels or protein hydrogels87-89. The Yang group rationally
designed a tetrameric protein (ULD-TIP-1) with four binding sites to a
peptide ligand90. Here, the ULD protein can form a very tight tetramer
structure and TIP-1 provides a peptide-binding site to hexa-peptide ligands
such as WRESAI. The peptide Nap-GFFYGGGWRESAI can self-assemble
into nanofibers (Fig. 11). However, this peptide does not form hydrogels.

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 Controlling peptide- based hydrogelation REVIEW

Fig. 10 (Left) Chemical structures of the precursor of the gelator (3) and the molecular gelator (4). (Right) Optical images showing a PBS buffer solution (pH = 7.4) of
4 (0.4 wt%, 2.42 mM) which forms a hydrogel on addition of reductants. Reproduced from Ren, C., et al., Chem Commun (2011) 47, 1619 with permission of The Royal
Society of Chemistry.

This was ascribed to the weak interactions between the self-assembled (a)
nanofibers. However, the addition of ULD-TIP-1 enhances interactions and
increases the cross-linking points between the nanofibers, thus leading
to hydrogelation. The mechanical properties could be manipulated in
several ways including the adjustment of peptide concentration, protein
concentration, and peptide sequence (peptides have different affinities to
the protein). The resulting hydrogels are shear-thinning and thixotropic, (b)
(d)
and hence are injectable. This hydrogel system could potentially be applied
for the delivery of therapeutic agents including proteins, cells, and drug
molecules.
(c)
Molecular hydrogelation via hydrolysis of
carboxylic ester bond (e)
(g)
The Xu and Yang groups recently reported that hydrophobic
molecules could only form hydrogels by a hydrolysis process catalyzed
by the phosphatase enzyme.5, 91 Recently, Xu reported another example of
molecular hydrogel of a hydrophobic small molecule92. They demonstrated (f)
a strategy of carboxylic ester bond hydrolysis as a means of forming a
hydrogel. 6 (Fig. 12) could not form clear solutions upon heating due
Fig. 11 Using a specific protein-peptide interaction to enhance interactions between
to its limited solubility and did not form gels on cooling. However, gels
self-assembled fibers thus leading to molecular hydrogelation: (a) the chemical
could be formed via a hydrolysis process from its precursor (7, Fig. 12). structure of Nap-GFFYGGGWRESAI. (b), (c), and (d) Nap-GFFYGGGWRESAI self-
The resulting gels of compound 6 were found to be stable over a wide pH assembled into nanofibers that lack strong interactions between fibers in aqueous
range. This strategy could also be applied for the generation of molecular solutions, resulting in a fiber network with a low density of cross-linking points. (e)
(f) and (g) the addition of the fusion protein (ULD-TIP-1) enhanced the interactions
hydrogels of hydrophobic therapeutic agents. For example, the Yang group
between fibers, leading to a 3D fiber network with high density of cross-links and
have reported a molecular hydrogel of taxol itself by the similar carboxylic hence hydrogel formation (scale bars in (b) and (e) represent 500 nm, the small balls
ester bond hydrolysis process93. The resulting molecular hydrogel of taxol in inserts of (d) and (g) represent the hydrophilic part of the molecule (GGGWRESAI).
was injectable and could be used for locally delivery of taxol to inhibit Reproduced from90 with permission from John Wiley and Sons.
tumors growth and metastasis. This strategy could lead to novel carrier-
free delivery systems of hydrophobic therapeutic agents.
alter the structure of the complementary peptide such that gels could
Mixing peptides be formed96. This was achieved by adjusting the peptide sequence to
Woolfson’s group have reported a number of mixed peptide systems place hydrogen-bonding glutamines on the surfaces of the coiled-coils. An
that form fibers when mixed94,95. This assembly only occurs when two alternative strategy of increasing the hydrophobicity of the surface also
complementary peptides are mixed. The single components do not led to gel formation. Gels were only formed in two component systems;
assemble. Unlike many of the examples in the sections above, the peptides single components did not lead to hydrogelation. This allows control
used adopt an α-helical conformation as opposed to β-sheets. The fibers over the assembly times. Circular dichroism and fiber X-ray diffraction
formed from mixing these complementary peptides do not generally lead confirmed the α-helical conformation. These gels supported cell growth
to gel formation. However, in 2009, it was shown that it was possible to and differentiation.

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REVIEW Controlling peptide- based hydrogelation

(a)

(b)

Fig. 12 (a) Synthetic pathway for the precursor of a gelator (6). Gels formed the precursor (7) formed (6) under basic conditions (pH 9) or via hydrolysis catalyzed by an
esterase (1U/μL,10 μL) at pH 7.5 (b) Optical images: left, normal; right, through a pair of crossed polarizers. Reprinted with permission from92. Copyright 2011 American
Chemical Society.

Fig. 13 Reaction cycle of the dissipative system. The dicarboxylate (top left) can react with MeI (fuel) to give monoester. This monoester can hydrolyse to form DBC or
react again with the fuel to form the diester. The diester can assemble into fibers, which will be in equilibrium between formation and hydrolysis of the diester until all the
MeI has reacted. Reproduced from97 with permission from John Wiley and Sons.

Chemical fuel
Boekhoven et al. recently published an interesting method of inducing
gel formation via addition of a chemical fuel as an energy source97. A
dibenzoyl-(L)-cystine precursor was converted into a gelator by alkylation
with methyl iodide, generating the methyl ester and thus leading to self-
assembly. The ester can be hydrolysed depending on the pH of the system.
At pH and 35 oC, ester formation was faster than hydrolysis. When the
diester is present at a sufficiently high concentration, gels can be formed.
These are however not stable over time since as soon as the source of
energy is consumed, hydrolysis to the diacid occurs and the system returns
to the non-aggregated state (Fig. 13).
Conclusions and outlooks
In our opinion, hydrogels formed from LMWG are currently relatively
under-exploited. This is possibly due to the very specific material properties
of the gels; they tend to break at relatively low strain as compared to
polymer-based hydrogels for example. However, there are many potential
advantages, including the reversibility of gel formation, the potential
biocompatibility of many LMWG, the low concentration of LMWG often
required to form a gel and the possibility to induce gelation using a range
of triggers. One complication is that the assembly of LMWG into nanofibers
and hence gel formation is very process-dependent. Hence, preparing gels
with reproducible properties requires careful control of the self-assembly.
There is a burgeoning volume of data showing how one can control the
assembly of range of LMWG, using triggers such as pH, salts and in situ
reduction. On the basis of this, we anticipate that LMWG will find many
applications in the near future. The potential for biomedical applications
is particularly high, especially with the development of enzymatic and
reductive methodologies. There are now many examples of cell culturing
on peptide-based LMWG hydrogels as well as recent demonstrations that
some drug molecules can themselves act as LMWG. We anticipate that
further biomedical-based use will soon follow.

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 Controlling peptide- based hydrogelation
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