Control of Stem-Cell Behavior by Fine Tuning the Supramolecular Assemblies of Low-Molecular-Weight Gelators

Article abstract of DOI:10.1002/anie.201409134

Controlling the behavior of stem cells through the supramolecular architecture of the extracellular matrix remains an important challenge in the culture of stem cells. Herein, we report on a new generation of low-molecular-weight gelators (LMWG) for the culture of isolated stem cells. The bola-amphiphile structures derived from nucleolipids feature unique rheological and biological properties suitable for tissue engineering applications. The bola-amphiphile-based hydrogel scaffold exhibits the following essential properties: it is nontoxic, easy to handle, injectable, and features a biocompatible rheology. The reported glycosyl-nucleoside bola-amphiphiles (GNBA) are the first examples of LMWG that allow the culture of isolated stem cells in a gel matrix. The results (TEM observations and rheology) suggest that the supramolecular organizations of the matrix play a role in the behavior of stem cells in 3D environments.

Full text of DOI:10.1002/anie.201409134

Angewandte
Chemie
DOI: 10.1002/anie.201409134
Hydrogels
Hot Paper
Control of Stem-Cell Behavior by Fine Tuning the Supramolecular
Assemblies of Low-Molecular-Weight Gelators**
Laurent Latxague, Michael A. Ramin, Ananda Appavoo, Pierre Berto, Mathieu Maisani,
Camille Ehret, Olivier Chassande, and Philippe Barthꢀlꢀmy*
Abstract: Controlling the behavior of stem cells through the
supramolecular architecture of the extracellular matrix
remains an important challenge in the culture of stem cells.
Herein, we report on a new generation of low-molecular-
weight gelators (LMWG) for the culture of isolated stem cells.
The bola-amphiphile structures derived from nucleolipids
feature unique rheological and biological properties suitable
for tissue engineering applications. The bola-amphiphile-based
hydrogel scaffold exhibits the following essential properties: it
is nontoxic, easy to handle, injectable, and features a biocom-
patible rheology. The reported glycosyl-nucleoside bola-
amphiphiles (GNBA) are the first examples of LMWG that
allow the culture of isolated stem cells in a gel matrix. The
results (TEM observations and rheology) suggest that the
supramolecular organizations of the matrix play a role in the
behavior of stem cells in 3D environments.
limitations, including poor biocompatibility, toxicity, biode-
gradability, proinflammatory activity etc. Alternatively, small-
molecule-based hydrogels, involving low-molecular-weight
gelators (LMWG), are emerging as a promising tool for
regenerative medicine strategy capable of restoring biological
and mechanical properties and/or function.[13]
Bola-amphiphiles are composed of one or two hydro-
phobic chains that are covalently linked at both ends to
hydrophilic head groups.[14] This type of molecular architec-
ture can be found in archaebacteria membranes,[15] and has
been used in numerous applications, ranging from nano-
material synthesis to drug or gene delivery.[16] The advantage
of using nucleosides in a bola-amphiphile design was first
described by Shimizu in 2002.[17] We hypothesized that bola-
amphiphile architectures could lead to LMWG-based hydro-
gels suitable for the culture of stem cells and tissue-engineer-
ing applications.
T
he development of biocompatible artificial matrixes that
Here, we report the first use of bola-amphiphile-based
hydrogels in the adhesion and proliferation of stem cells.
Contrary to the previously reported glycosyl-nucleoside lipids
(GNL)[18] and glycosyl-nucleoside fluorinated amphiphile
(GNF),[13] which suffer from biological and rheological
limitations, the glycosyl-nucleoside bola-amphiphiles
(GNBA) offer a new biocompatible microenvironment for
the culture of stem cells. GNBA-based gels feature improved
mechanical properties, including a stiffness that allows
a process called mechanotransduction,[19] which is required
for tissue-engineering applications (Figure 1).
The synthesis of GNBAs 1, 2, and 3 (depicted in
Scheme 1) relies mainly on a double click-chemistry strategy
as used in most of our earlier works (see the Supporting
Information for details). For compounds 1 and 2, gel
formation was observed in water at 1% (w/v). On the other
hand, bola-amphiphile 3 was unable to stabilize a gel,
indicating that nucleoside moiety is required for gel stabiliza-
tion. Transmission electron microscopy (TEM) images of the
hydrogel obtained from GNBA 1 show the formation of an
anisotropic fibrillar network. This network is densely inter-
connected through straight fibers of 6–9 nm in width (see the
Supporting Information, Figure S3A), which likely contribute
to the high storage modulus that can be observed. Note that
under similar conditions, dissymmetric bola-amphiphile 2 and
GNF exhibit bundles of nanofibers with fewer connections
(see the Supporting Information, Figure S3B and Fig-
ure S3C).
can be used for the culture of stem cell remains a great
challenge in tissue engineering and/or regenerative medi-
cine.[1–5] Recent studies in these promising fields have focused
on understanding the physicochemical parameters that con-
trol the fate of stem cells.[6,7] While several studies have
concentrated on the impact of biochemical cues on the
behavior of stem cells, it has been demonstrated that the
mechanical properties of the microenvironment play a major
role on a wide variety of cells including stem cells.[8] The
matrix stiffness is known to affect the behavior of cardiac
cells,[9] glial cells[10] and mesenchymal stem cells.[11,12] Most of
these studies used gel scaffolds based on polymeric materials
that were derived from either natural sources or chemical
synthesis. However, polymers often suffer from several
[*] Dr. L. Latxague, Dr. M. A. Ramin, A. Appavoo, P. Berto,
Prof. P. Barthꢀlꢀmy
Univ. Bordeaux, ARNA laboratory, F-33000 Bordeaux (France)
E-mail: philippe.barthelemy@inserm.fr
M. Maisani, C. Ehret, Dr. O. Chassande
INSERM, U1026, BIOTIS laboratory, F-33000 Bordeaux (France)
[**] The authors acknowledge financial support from the French
National Agency (ANR) in the frame of its program Blanc “GelCells”
SIMI 7-2010 and the Conseil Rꢀgional d’Aquitaine (CRAq). We
acknowledge the Army Research Office for financial support. The
authors would like to thank Andrew Goldsborough and Brice
Kauffmann for proof-reading the MS and SAXS experiments,
respectively.
To further understand the molecular organization and
packing profile within the supramolecular structures, small-
angle X-ray scattering (SAXS) experiments were performed
at room temperature. The small-angle diffraction patterns of
Supporting information for this article (including experimental
procedures and characterization data, such as NMR, MS, and DLS
results, and TEM images) is available on the WWW under http://dx.
doi.org/10.1002/anie.201409134.
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Scheme 1. Structures of bola-amphiphiles synthesized for this study, compared with glycosyl-nucleoside fluorinated amphiphile (GNF).
[D6]DMSO (Figure 2). The addition of
water to the sample led to an upfield shift
of the triazole hydrogen atom and the
thymidine hydrogen atom H-5’, which indi-
cates the contribution of both triazole and
nucleobase p–p stacking to the aggregation
phenomenon. The temperature-dependent
1H NMR study also confirms the presence of
p–p stacking interactions between the aro-
matic moieties. In this case, these signals are
deshielded with the increase in temperature
(see the Supporting Information, Figure S2).
The mechanical behavior of our hydro-
gels was estimated by rheology. All rheo-
logical experiments were conducted within
Figure 1. Formation of the LMWG scaffold suitable for the culture of stem cells. GNBA self-
assemble through six p–p interactions per molecule to provide stable and straight fibers.
The resulting self-healing hydrogels feature stiffness properties, which allow the adhesion
and proliferation of stem cells. Scale bar: 200 nm.
the linear viscoelastic region. We studied the
variation of storage modulus (G’) and loss
modulus (G’’) as a function of the applied
frequency. The storage modulus (G’), also
called the elastic modulus, describes the
aqueous samples (GNBA 1 at 30%, w/v) show a diffraction
peak at 3.1 nm (see the Supporting Information, Figure S4).
This repeat period, which corresponds roughly to the
molecular length of GNBA 1 (4 nm in extended conforma-
tion, calculated by MM + force field modeling), suggests that
two molecules are tightly associated in the thin fibers.
The molecular scaffold of the gel is formed through
noncovalent interactions, such as hydrogen bonds, p–p
stacking interactions, van der Waals interactions etc.[20]
Interestingly, GNBAs contain, among other groups, a 1,2,3-
triazole ring and a nucleoside, which can be involved in the
formation of supramolecular assemblies.[21] To highlight their
role in the self-assembly process, an NMR study was realized
by adding water to a solution of bola-amphiphiles 1 and 2 in
amount of the energy that is stored and released in each
oscillation. The loss modulus (G’’), also called the viscous
modulus, corresponds to the energy dissipated as heat (and
therefore lost). For all our hydrogels, the storage modulus
exceeded that of the loss modulus and their values were
weakly dependent on the frequency in the entire range that
we tested, which indicates the formation of a stable gel
(Figure 3).
In order to evaluate the relative strength of the hydrogels,
we compared the storage moduli at an angular frequency of
1 radsÀ1. The G’ value for hydrogel 1 (30325 Pa) is much
higher than the value obtained for the GNF hydrogel
(1749 Pa) at the same concentration (11.55 mm). This obser-
vation suggests the formation of a more rigid and “solid-like”
2
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Figure 2. Partial 1H NMR spectra of GNBA (compound 1) showing the
resonance signals of triazole and H5’-thymidine hydrogen atoms.
Spectra were recorded in [D6]DMSO (7 mg of compound 1 in 0.5 mL
[D6]DMSO) with increasing amounts of water.
Figure 4. Step–strain measurement of the hydrogel 1 at 1% (w/v) at
a fixed angular frequency of 6.283 rad/s. The gel was successively
swept from 0.03% to 15% strain, then back to 0.03% strain.
the G’ value was much lower indicating the collapse of the gel,
that is, the gel liquefies under the stress. With a strain of
0.03% (as in the first step), the sample gradually returns to
the gel state and recovers its original strength. Indeed, the G’
value increases rapidly and the sample recovers approxi-
mately 80% of its initial elastic modulus within 15 min. This
experiment was repeated at least three times to verify its
reproducibility (see the Supporting Information, Figure S7).
The therapeutic applicability of the thixotropic behavior of
GNBA-based gel was challenged in a mouse model using
subcutaneous injection. The GNBA solution was drawn into
a syringe and left at room temperature until gelation. Then
the gel was pushed with the piston through a 16-gauge needle,
resulting in a gel–sol transition that allowed the injection of
the solution under the skin of an anaesthetized mouse (see
movie, see the Supporting Information). 2 h after injection,
a superficial examination of the tissue after skin biopsy
showed the presence of a bulk of gel that displayed an ovoid
shape and was easily distinguishable from the surrounding fat
tissue. Sections showed the gel structure as small fibers that
did not contain any cells or matrix surrounded by host tissue
(see the Supporting Information, Figure S11). This experi-
ment emphasizes the injectability of the GNBA gel by taking
advantage of its thixotropic property.
In order to evaluate the biocompatibility of the GNBA 1,
we carried out cytotoxicity and cytocompatibility studies. For
this purpose, human mesenchymal stem cells isolated from
adipose tissue (ASC) were grown for four days in the
presence of GNBA at increasing concentrations. The toxicity
was evaluated by a MTT test (colorimetric assay for assessing
cell viability using a tetrazolium dye). No toxicity was found
for concentrations up to 50 mm (see Supporting Information,
Figure S8).
In order to evaluate the behavior of cells in the LMWG
matrixes, different cell types were embedded in the GNBA
gel (3% GNBA, w/v). The GNBA gels were initially prepared
without cells and heated at 558C for 30 min to obtain a liquid
phase. After cooling to 378C, the cells were mixed with the
GNBA solution and the mixture was incubated at 258C under
gentle stirring.
Figure 3. Frequency sweep results for hydrogels obtained from com-
pound 1 and GNF (at 11.55 mm) at a constant strain of 0.03%.
material with the hydrogel obtained from the symmetrical
bola-amphiphile. The elastic character is significantly
improved with the GNBA 1 compared to the GNF analogue.
However, the elastic modulus is much lower with the unsym-
metrical bola-amphiphile 2 (see the Supporting Information,
Figure S6) at the same concentration (23.10 mm). This result
may be explained by fewer interactions between the nucleo-
side and triazole moieties of compound 2 (three p–p stacking
interactions instead of six for GNBA 1).
For some biomedical applications, a hydrogel should be
delivered by syringe, thereby preventing the pain of a surgical
implantation.[22] Therefore, this injectable hydrogel must
regain its strength after the injection (the withdrawal of
external stress). The gel obtained from compound 1 can be
shaken vigorously by hand and the sample immediately
recovers its gel behavior. This thixotropic property was
studied in more detail by rheology. The experiment consists
in applying a high strain to the sample and studying the
evolution of the viscoelastic moduli (Figure 4). First, a low
strain of 0.03% was applied to gel 1 at 1% (w/v) for 20 min. In
the gel state, G’ was larger than G’’. Then, gel 1 was suddenly
subjected to a higher strain of 15% for 2 min. At this point,
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The rat preosteoblastic cell line D1 was first grown within
the gel. The cell concentration was longitudinally followed
using a nontoxic metabolic activity assay with alamar blue.
This analysis showed a moderate increase of the number of
cells over two weeks. The same experiment was performed
with human ASCs, showing a stability of the number of cells,
with a slight decrease two weeks after seeding (see the
Supporting Information, Figure S9). Altogether these data
show that neither low concentrations of soluble GNBA nor
high GNBA concentrations, which could result in gel
formation, have toxic effects on cells.
would be very useful for applications in regenerative medi-
cine and tissue engineering.
Received: September 15, 2014
Revised: November 5, 2014
Published online: && &&, &&&&
Keywords: amphiphiles · hydrogels · stem cells ·
.
supramolecular chemistry
The human ASCs cells embedded in the gels were
examined by confocal microscopy and submitted to a live–
dead assay to assess the cell viability. In the case of GNBA 1,
24 h after seeding, all cells were attached to the gel scaffold
and were viable (Figure 5). Most of the cells appeared round,
[1] a) J. H. Wen, L. G. Vincent, A. Fuhrmann, Y. Choi, K. C. Hribar,
H. Taylor-Weiner, S. Chen, A. J. Engler, Nat. Mater. 2014, 10,
979 – 987; b) F. Rossi, M. Santoro, G. Perale, J. Tissue Eng.
Regen. Med. 2013, DOI: 10.1002/term.1827; c) K. A. Kilian, M.
Mrksich, Angew. Chem. Int. Ed. 2012, 51, 4891 – 4895; Angew.
Chem. 2012, 124, 4975 – 4979.
[2] S. Gemini-Piperni, E. R. Takamori, S. C. Sartoretto, K. B. S.
Paiva, J. M. Granjeiro, R. C. de Oliveira, W. F. Zambuzzi, Arch.
Biochem. Biophys. 2014, 561, 88 – 98.
[3] J. Xiong, M. Onal, R. L. Jilka, R. S. Weinstein, S. C. Manolagas,
C. A. OꢀBrien, Nat. Med. 2011, 17, 1235 – 1241.
[4] a) S. Shah, A. Solanki, P. K. Sasmal, K. B. Lee, J. Am. Chem. Soc.
2013, 135, 15682 – 15685; b) D. R. Griffin, A. M. Kasko, J. Am.
Chem. Soc. 2012, 134, 13103 – 13107; c) M. He, J. Li, S. Tan, R.
Wang, Y. Zhang, J. Am. Chem. Soc. 2013, 135, 18718 – 18721.
[5] B. P. Purcell, D. Lobb, M. B. Charati, S. M. Dorsey, R. J. Wade,
K. N. Zellars, H. Doviak, S. Pettaway, C. B. Logdon, J. A.
Shuman, P. D. Freels, J. H. Gorman III, R. C. Gorman, F. G.
Spinale, J. A. Burdick, Nat. Mater. 2014, 13, 653 – 661.
[6] O. Z. Fisher, A. Khademhosseini, R. Langer, N. A. Peppas, Acc.
Chem. Res. 2010, 43, 419 – 428.
[7] A. Banerjee, M. Arha, S. Choudhary, R. S. Ashton, S. R. Bhatia,
D. V. Schaffer, R. S. Kane, Biomaterials 2009, 30, 4695 – 4699.
[8] J. Kim, Y. Park, G. Tae, K. B. Lee, C. M. Hwang, S. J. Hwang, I. S.
Kim, I. Noh, K. Sun, J. Biomed. Mater. Res. Part A 2009, 88, 967 –
975.
Figure 5. Pictures of GNBA-gel-embedded human ASCs grown for 24 h
or 7 days (obtained by stacking of 10 images, representing 100 mm
thickness in the z axis). The top white arrow points to a dividing cell.
The bottom white arrow points to a fibroblastoid cell. Cells are stained
green (calcein), wheras the GNBA gel is stained red, as it incorporates
the ethidium molecule. Scale bar: 200 mm.
[9] P. Bajaj, X. Tang, T. A. Saif, R. Bashir, J. Biomed. Mater. Res.
Part A 2010, 95, 1261 – 1269.
[10] H. Mori, A. Takahashi, A. Horimoto, M. Hara, Neurosci. Lett.
2013, 555, 1 – 6.
[11] A. J. Engler, S. Sen, H. L. Sweeney, D. E. Discher, Cell 2006, 126,
677 – 689.
[12] A. S. Khalil, A. W. Xie, W. L. Murphy, ACS Chem. Biol. 2014, 9,
45 – 56.
[13] a) G. Godeau, C. Brun, H. Arnion, C. Staedel, P. Barthꢁlꢁmy,
Tetrahedron Lett. 2010, 51, 1012 – 1015; b) S. Ziane, S. Schlau-
bitz, S. Miraux, A. Patwa, C. Lalande, L. Bilem, S. Lepreux, B.
Rousseau, J.-F. Le Meins, L. Latxague, P. Barthꢁlꢁmy, O.
Chassande, eCM 2012, 23, 147 – 160.
[14] a) L. A. Estroff, A. D. Hamilton, Chem. Rev. 2004, 104, 1201 –
1218; b) M. Brard, M. Richter, T. Benvegnu, D. Plusquellec, J.
Am. Chem. Soc. 2004, 126, 10003 – 11012; c) A. Meister, A.
Blume, Curr. Opin. Colloid Interface Sci. 2007, 12, 138 – 147;
d) Y. Yan, T. Lu, J. Huang, J. Colloid Interface Sci. 2009, 337, 1 –
10; e) A. Meister, A. Blume, Adv. Planar Lipid Bilayers 2012, 16,
93 – 128; f) A. Blume, S. Drescher, G. Graf, K. Kçhler, A.
Meister, Adv. Colloid Interface Sci. 2014, 208, 264 – 278.
[15] J. H. Fuhrhop, T. Wang, Chem. Rev. 2004, 104, 2901 – 2937.
[16] a) J. Gaucheron, C. Santaella, P. Vierling, Bioconjugate Chem.
2001, 12, 569 – 575; b) M. Brunelle, A. Polidori, S. Denoyelle, A.-
S. Fabiano, P. Y. Vuillaume, S. Laurent-Lewandowski, B. Pucci,
C. R. Chim. 2009, 12, 188 – 208; c) N. Jain, V. Goldscmidt, S.
Oncul, Y. Arntz, G. Duportail, Y. Mꢁly, A. S. Klymchenko, Int. J.
Pharm. 2012, 423, 392 – 400; d) N. Nuraje, H. Bai, K. Su, Prog.
Polym. Sci. 2013, 38, 302 – 343.
however, some cells exhibited a fibroblastoid phenotype,
typical of cell adhesion. One week after seeding, the cells had
scattered within the gel and most of them showed a fibro-
blastoid morphology. A vast majority of green (living) cells
was found. Cell divisions were occasionally observed, too. In
contrast, in the case of the GNF hydrogel, which exhibited
weak stiffness properties (G’ = 1.7 kPa), isolated cells showed
a round morphology and failed to survive over four days (see
the Supporting Information, Figure S10). As GNBA 1 and
GNF share the hydrophilic moieties glucose and thymidine,
the more favorable behavior of stem cells in GNBA gels can
be attributed to the 3D organization of the scaffold. This is
characterized by a higher mechanical resistance (GNBA, G’ =
30 kPa), which promotes cell adhesion and spreading.[23]
In summary, we have developed a scalable synthesis of
self-healing hydrogels using glycosyl-nucleoside bola-amphi-
philes as low-molecular-weight gelators (LMWG). These
biocompatible hydrogels feature a high elastic modulus,
which allows the adhesion and the proliferation of isolated
stem cells. To our knowledge, this is the first time that the
influence of the modulus of LMWGs on the fate of stem cells
was demonstrated. Three-dimensional scaffolds based on
biocompatible LMWGs that control the fate of stem cells
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[17] a) R. Iwaura, K. Yoshida, M. Masuda, K. Yase, T. Shimizu,
Chem. Mater. 2002, 14, 3047 – 3053; b) R. Iwaura, K. Yoshida, M.
Masuda, M. Ohnishi-Kameyama, M. Yoshida, T. Shimizu,
Angew. Chem. Int. Ed. 2003, 42, 1009 – 1012; Angew. Chem.
2003, 115, 1039 – 1042.
Chem. Rev. 1997, 97, 3133 – 3159; c) S. Banerjee, R. K. Das, U.
Maitra, J. Mater. Chem. 2009, 19, 6649 – 6687; d) D. J. Abdallah,
R. G. Weiss, Adv. Mater. 2000, 12, 1237 – 1247.
[21] M. J. Clemente, P. Romero, J. L. Serrano, J. Fitremann, L. Oriol,
Chem. Mater. 2012, 24, 3847 – 3858.
[18] a) G. Godeau, J. Bernard, C. Staedel, P. Barthꢁlꢁmy, Chem.
Commun. 2009, 5127 – 5129; b) L. Latxague, S. Ziane, O.
Chassande, A. Patwa, M.-J. Dalila, P. Barthꢁlꢁmy, Chem.
Commun. 2011, 47, 12598 – 12600.
[19] T. A. Ulrich, A. Jain, K. Tanner, J. L. MacKay, S. Kumar,
Biomaterials 2010, 31, 1875 – 1884.
[22] a) B. D. Olsen, J. A. Kornfield, D. A. Tirrell, Macromolecules
2010, 43, 9094 – 9099; b) W. Wang, L. Deng, S. Xu, X. Zhao, N.
Lv, G. Zhang, N. Gu, R. Hu, J. Zhang, J. Liu, A. Dong, J. Mater.
Chem. B 2013, 1, 552 – 563; c) A. Baral, S. Roy, A. Dehsorkhi,
I. W. Hamley, S. Mohapatra, S. Ghosh, A. Banerjee, Langmuir
2014, 30, 929 – 936; d) J. Nanda, A. Biswas, A. Banerjee, Soft
Matter 2013, 9, 4198 – 4208.
[20] a) B. Xing, C.-W. Yu, K.-H. Chow, P.-L. Ho, D. Fu, N. Xu, J. Am.
Chem. Soc. 2002, 124, 14846 – 14847; b) P. Terech, R. G. Weiss,
[23] B. J. Lawrence, S. V. Madihally, Adhes. Migr. 2008, 2, 9 – 16.
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Communications
Hydrogels
L. Latxague, M. A. Ramin, A. Appavoo,
P. Berto, M. Maisani, C. Ehret,
O. Chassande,
P. Barthꢁlꢁmy*
&&&& — &&&&
Culture medium: Glycosyl-nucleoside
bola-amphiphiles (GNBAs) are low-
molecular-weight gelators that allow the
culture of isolated stem cells in a gel
matrix. The reported results highlight the
role of the supramolecular organizations
of the matrix on the behavior of stem cells
in 3D environments.
Control of Stem-Cell Behavior by Fine
Tuning the Supramolecular Assemblies of
Low-Molecular-Weight Gelators
6
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!