The Cooperative Effect of Both Molecular and Supramolecular Chirality on Cell Adhesion

Article abstract of DOI:10.1002/anie.201801462

Although helical nanofibrous structures have great influence on cell adhesion, the role played by chiral molecules in these structures on cells behavior has usually been ignored. The chirality of helical nanofibers is inverted by the odd–even effect of methylene units from homochiral l-phenylalanine derivative during assembly. An increase in cell adhesion on left-handed nanofibers and weak influence of cell behaviors on right-handed nanofibers are observed, even though both were derived from l-phenylalanine derivatives. Weak and negative influences on cell behavior was also observed for left- and right-handed nanofibers derived from d-phenylalanine, respectively. The effect on cell adhesion of single chiral molecules and helical nanofibers may be mutually offset.

Full text of DOI:10.1002/anie.201801462

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: The Role of Chiral Molecules in Helical Nanofibers on Cell
adhesion
Authors: Jinying Liu, Feng Yuan, Xiaoyu Ma, Y. Auphedeous Dang-i,
Changli Zhao, Chuntai Liu, Changyu Shen, and Chuan Liang
Feng
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201801462
Angew. Chem. 10.1002/ange.201801462
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10.1002/anie.201801462
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The Cooperative Effect of both Molecular and Supramolecular
Chirality on Cell Adhesion
Jinying Liu,[a] Feng Yuan,[a] Xiaoyu Ma,[a] Dang-i Y. Auphedeous,[a] Changli Zhao,[a] Chuntai Liu,[b]
Changyu Shen[b] and Chuanliang Feng*[a]
Dedication ((optional))
Abstract: Although helical nanofibrous structures have great
influence on cell adhesion, the role played by chiral molecules in
these structures on cells behavior is usually ignored and still
unclear. In this paper, the chirality of helical nanofibers is
inverted by odd−even effect of methylene units from homochiral
L-phenylalanine derivative during assembly. An increase in cell
adhesion on left-handed nanofibers and weak influence of cell
behaviors on right-handed nanofibers are observed, even
though both were derived from L-phenylalanine derivatives.
Weak and negative influences on cell behaviour was also
observed for left and right handed nanofibers derived from D-
phenylalanine respectively. It is considered that the effect on cell
adhesion of single chiral molecules and helical nanofibers may
be mutually offset. This study not only presents a viable strategy
to achieve the handedness inversion of helical nanostructures
by the odd-even effect, but also provides a method to touch the
fundamental problems for the studies in the origins of life and
the high chiral preference of life.
biomacromolecules fabricated with homochiral small molecules,
such as L-amino acids (except glycine) and D-saccharides,
controllable helical supramolecular assemblies constructed with
enantiomers are averse to mimic helical inversion events of
these biomacromolecules and elucidate their specific bio-
functional transformation.
To address this issue, it is helpful to use only one enantiomer
to construct supramolecular architectures with controlled helical
chirality and favorable biocompatibility, where handedness
inversion of the self-assemblies would be triggered by achiral
factors. Although many chirality inversions of supramolecular
assemblies have been mediated by achiral factors, such as a
change in solvent[8] or temperature,[9] light irradiation,[5a, 10] slight
structural change,[11] addition of chemical species[12] and rotary
stirring,[13] these existing helical inversion of supramolecular
nanostructures are still far behind biomolecular systems in terms
of biocompatibility and functionality. It is known that the odd-
even effect could successively change a property just through
varying the position or number of a structural element from an
odd number or an even number. Recently, the ability to change
gels and the morphology of supramolecular structures with the
odd-even effect has been reported,[14] however, using odd-even
effect to tune the handedness of supramolecular nanostructures
transitioning them between P and M is rarely reported.[15]
Helical architectures (e.g., DNA or proteins) are present in
many biomolecular systems, where they occasionally perform
helicity inversion in many physiological processes along with
specific biofunctional transformations.[1] Pioneering researches
reveal that the handedness of nanoarchitectures not only have a
profound effect on stem cell differentiation, cell adhesion and
protein adhesion,[2] but also applicatications in areas of sensing
or recognition,[3] catalysis,[4] chiroptical switches,[5] and
medicine.[6] Although the helical chirality of nanoscale
architectures is significant in biomaterial and relevant biological
studies, these helical assemblies are usually fabricated with
enantiomeric building blocks, and the enantiomeric effect of the
single molecule cannot be shielded when searching for their
biological functions.[2b,c] This ascribes to the property of the
molecular chirality which can be kept or amplified upon forming
these helical assemblies, besides single chiral molecule usually
reveals opposite influence in many biological events depending
on their chirality.[7] In view of the basic building blocks of
[a]
Jinying Liu, Feng Yuan, Xiaoyu Ma, Dang-i Y. Auphedeous,
Changli Zhao and Prof. C. L. Feng
State Key Lab of Metal Matrix Composites
School of Materials Science and Engineering
Shanghai Jiao Tong University, Shanghai 200240, China
E-mail: clfeng@sjtu.edu.cn
[b]
Chuntai Liu, Changyu Shen
National Engineering Research Center for Advanced Polymer
Processing Technologies, Zhengzhou University, Zhengzhou,
China
Scheme 1. Chemical structure of BA, BE and BP, and schematic illustration of
helical chirality inversion tuned by the variable methylene units.
Supporting information for this article is given via a link at the end
of the document. ((Please delete this text if not appropriate))
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10.1002/anie.201801462
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Herein, chirality regulation of hydrogels self-assembled from
C2-symmetric hydrogelators through odd−even effect of
methylene units are studied (n=0, 1, 2). The chirality of the
assembled nanofiber depends on n, which can form right-
handed (P-type) nanofibers if methylene number is even (n=0,
BA; n=2, BP) and left-handed (M-type) nanofibers if it is odd
(n=1, BE) (Scheme 1). Mouse embryonic fibroblast cell line
( NIH 3T3) and human-derived EA.hy926 endothelial cells
(Hy926) were used to investigate cell adhesion and proliferation
on two-dimension (2D) films. The cell densities of fibroblast cells
and endothelial cells on BE film are 1.2-folds and 1.3-folds as
high as those on BA and BP film, respectively. The results show
an increase in cell adhesion and proliferation with left-handed
nanofibers, whereas right-handed nanofibers have weak
influence, even though these nanofibers are all assembled from
L-phenylalanine derivatives. The result suggests that the effect
on cell adhesion of single chiral molecules and helical
nanofibers may be mutually offset. This finding provides novel
insight into touching the fundamental problems for the studies in
the origins of life and the high chiral preference of life.
produced right-handed twisted nanofibers. The diameter and
helical pitch of BA nanofibers are ~80 nm and ~1.5 μm (Figure
1B), ~310 nm and ~2.2 μm for BP (Figure 1D), respectively.
However, well-defined left-handed twisted nanofibers with the
diameter of 155 nm and helical pitch of 1.6 μm were observed
for BE nanofibers (Figure 1C). Here, all the hydrogelators
possess the same S-type stereo center within the peripheral L-
phenylalanine units, thus, the chiral inversion was obviously
triggered by methylene numbers and the variable methylene
units slightly alter the conformation of the disk in the stack,
inducing a small change in the pitch and diameter of the helix.
Left-handed and right-handed nanofibers of the D-enantiomer of
BA and BE were also observed from the SEM images
respectively ( Figure S 13 c and d).
The syntheses of BA, BE and BP are outlined in Supporting
Information (Scheme S1-S3), similar to previously published
strategies. All the newly reported compounds have been fully
characterized by NMR and high-resolution mass spectrometry
(Supporting Information). The ability of compounds BA, BE and
BP to self-assemble into hydrogels was tested in distilled water
(milli Q). The hydrogel formation was judged by the “invert-vial”
method (Figure S1), and the rheological properties of hydrogels
were measured using
a rotary rheometer with dynamic
frequency sweep at a strain of 0.01%. The higher values of
elastic modulus (G’) than those of viscous modulus values (G’’)
further indicated the formation of solid gels (Figure S3).
Figure 2. A) CD spectra of the BA, BE and BP, hydrogels were obtained by
using a 0.1 mm quartz cuvette with a total gelator concentration of 2.0 mg/mL
BA, 3.0 mg/mL BE and 9.0 mg/mL BP (with 3% DMSO in water), B) VCD
spectra of the BA, BE and BP xerogel.
The helicity of the aggregates formed by BA, BE and BP in gel
state was investigated by CD spectroscopy at room temperature
(Figure 2A). The CD spectrum of BA (Figure 2A top) in water
shows significant Cotton effect with an isodichroic point, zero
crossing at 239 nm, and a strong positive (273 nm) and weak
negative (228 nm) CD signals. Similarly, weak positive Cotton
effects (273 nm) and strong negative CD signals (215 nm) were
observed for BP (Figure 2A bottom). However, as expected, the
Cotton effect of BE is opposite in sign compared with BA and BP.
The CD spectra of the BE (Figure 2A middle) clearly showed the
bisignated Cotton effect with a positive maximum at 227 nm and
a negative maximum at 240 nm. The CD signal of BA, BE and
BP showed a clear sign inversion with odd-even number
methylene units placed between the chiral center and benzene
group, which is in good agreement with SEM results. It must be
pointed out that the structure of BA, BE and BP have slight
change, so their CD spectra should not be exact mirror images.
CD spectra for the D-enantiomer of BA and BE further confirmed
Figure 1. A) Schematic illustration of twisted nanofiber BA、 BE and BP, M
and P denote left- and right-handed helical or twisted nanofibers, respectively.
B) SEM images of right-handed helical fibers in the BA xerogel, C) SEM
images of left-handed helical fibers in the BE xerogel, D) SEM images of right-
handed helical fibers in the BP xerogel.
To investigate the morphology of nanostructures self-
assembled from BA, BE and BP, SEM images were employed.
BA and BP with an even number of methylene units (n=0, 2)
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10.1002/anie.201801462
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the chirality inversion caused by the number change in
methylene units (Figure S 13 b).
The chiroptical activities of these hydrogels were also
investigated by vibrational circular dichroism (VCD, Figure 2B).
BA (Figure 2B top) and BP (Figure 2B bottom) exhibited a same
for 4 h, the quantity of adhered live cells on the BE films was 1.2
times and 1.3 times as high as that on the BA films and BP films,
respectively (Table S2), and showed well spreading morphology,
which indicated good cell adhesion. While cell number on the BA
and BP films was not statistically different compared with the
(-/+) signal of C=O stretching band between 1750 and 1600 cm-1, controlled PS plate (Figure S8). At the next four time points, cell
conversely the VCD signal of BE showed a significant (+/-)
pattern between 1700 and 1600 cm-1 (Figure 2B middle). Hence,
a strong and extensive C=O•••HN hydrogen-bonding network,
significantly stabilizing the supramolecular hydrogels of BA, BE
and BP, is inferred from the vibrational amide I stretching band
at around 1636 cm-1. The VCD patterns imply the inversion of
the chirality from BA to BE to BP, which may be ascribed to the
different number of methylene units. This is in congruence with
SEM and CD experiments, which show that BA have right-
handed nanofibers, BE, left-handed nanofibers and BP, right-
handed nanofibers.
In the view that surface wettability of the xerogels has a great
influence on cell adhesion and protein adsorption,the surface
hydrophilic properties of the xerogels membrane of BA、BE and
BP were characterized by contact angles (Figure S4), 38.3o±
2.9o for BA, 45.5o±3.7o for BE and 46.5o±3.4o for BP, indicating
a similarity in wettability. This is ascribed to the peripheral group
with uniform hydrophilic 2-(2-Aminoethoxy)ethanol for the three
gelators.
growth density was found to be proportional to the original
adhesion density for each film (Figure 3 and Figures S8),
indicating better cell adhesion is the critical prerequisite for
gaining higher cell proliferation. The good cytocompatibility of
the nanofibers was also proved by a live–dead staining assay
(see Figure S7). To further confirm the chirality effect of the
nanofiber on different cell type, endothelial cells Hy926 were
plated on the different films (ca. 2000 cells per well). The results
were similar to those observed on the NIH 3T3 cells, i.e. both
the cell-adhesion and cell-proliferation density on BE films was
about 1.2 times as high as that on the BA films and about 1.3
times as high as that on BP films (Table S3 and Figures S10
and S11). These results demonstrated left-handed helical
nanofibers can increase cell adhesion and proliferation whiles
right-handed nanofibers had weak influence, even though both
nanofibers were derived from L-phenylalanine derivatives. Also,
the stereospecific interaction between the cells and these chiral
nanofibers is a common effect that can be applied to different
cell types. We went ahead to confirm the effect of molecular and
supramolecular chirality on cell adhesion and proliferation by
seeding the mouse embryonic fibroblasts NIH 3T3 (ca. 2000
cells per well) on the D-enantiomer of BA and BE (d-BA and d-
BE respectively). The results showed a weak influence on cell
behavior by left-handed nanofibers from D- phenylalanine (d-BA)
and a negative influence on cell behavior by right-handed
nanofibers from D- phenylalanine (d-BE) (Figure S14, S15 and
Table S4).
Scheme 2. A) Positive effect on cell adhesion on left-handed nanofibers
derived from L-phenylalanine derivative; B, C) Weak effect on cell adhesion on
right-handed nanofibers derived from L-phenylalanine derivative and left-
handed nanofibers derived from D-phenylalanine derivative; D) Negative effect
on cell adhesion on right-handed nanofibers derived from D-phenylalanine
derivative.
Figure 3. A) Fluorescence microscopy images of Hy926 cells after culture for
5 days (a, b, c and d) and NIH 3T3 cells after culture for 3 days (e, f, g and h)
on BA, BE, and BP nanofiber films and PS Control well. Scale bar: 100 μm.
B,C) Quantitative data for Hy926 cells (B) and NIH 3T3 cells (C) on BA, BE,
and BP nanofiber films and PS Control well after incubation for 4 h, 1 day, 2
days, 3 days, 5 days, and 7 days. N=6; *, **, *** data show significant
differences (ANOVA: *p0.05, ** p0.005, *** p0.001).
Our previous work has proved that left-handed helical
nanofibers self-assembled from L-phenylalanine derivative have
positive effect on fibroblast and endothelial cell adhesion. On the
contrary, the right-handed nanofibers derived from D-
phenylalanine derivative induced a decrease in cell adhesion
density (Scheme 2A, 2D).[2c] It ascribes to the kept or amplified
property of D-enantiomer chirality upon forming helical
assemblies, while, it proves that D-enantiomer modified surfaces
To assess the effect of chiral nanofibers arising from BA、BE
and BP on cell-adhesion and cell-proliferation behavior, mouse
embryonic fibroblasts NIH 3T3 cells were seeded (ca. 2000 cells
per well) on a two dimensional (2D) substrate coated with BA,
BE, and BP nanofiber films, and the polystyrene (PS) well was
o
used as control. The cells were incubated at 37 C and 5% CO2
for 4 hours, 1 day, 2 days, 3 days, and 5 days. After incubation
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[3]
[4]
a) K. Kodama, Y. Kobayashi, K. Saigo, Chem. Eur. J. 2007, 13, 2144-
2152; b) W. Edwards, D. K. Smith, J. Am. Chem. Soc. 2014, 136, 1116-
1124; c) S. M. So, K. Moozeh, A. J. Lough, J. Chin, Angew. Chem. Int.
Ed. 2014, 53, 829-832; d) L. Zhang, L. Qin, X. Wang, H. Cao, M. Liu,
Adv. Mater. 2014, 26, 6959-6964.
are not favorable for cell adhesion compared with L-enantiomer
surfaces.[7a,7c,7f] Herein, L-phenylalanine chiral property should
also be kept in the right-handed helical nanofibers derived from
L-phenylalanine derivatives. Although cells prefer to interact with
L-enantiomer molecules, the right-handed nanofibers have
opposite influence on cell adhesion. This mutual offsetting leads
to the weak influence on cell adhesion on the right-handed BA
and BP nanofibers (Scheme 2B). In a similar manner, left
handed nanofibers from the D-enantiomer molecule d-BA
displayed a weak influence on cell adhesion (Scheme 2C，
Figure S14-15 and Table S4). Thus, it is considered that the
design of helical nanofibers with homochiral small molecules
(e.g., L-amino acids, D-saccharides) may bring a novel direction
for biomaterial design, which is helpful to touch the fundamental
problems for the studies in the origins of life and the high chiral
preference of life.
In conclusion, the helicity inversion of supramolecular
assemblies based on C2 symmetric L-phenylalanine derivatives
has been successfully achieved through inserting variable
methylene units between the chiral center and rigid aromatic
core. It shows an increase in cell adhesion and proliferation on
left-handed nanofibers and weak influence on cells behaviors on
the right-handed nanofibers, though both types of helical
nanofibers are derived from L-phenylalanine derivatives. The
results provide some initial design rules for constructing helical
supramolecular architechture with homochiral small molecules
through the odd-even effect. Typically, this tunable helical
chirality system also paves a new way to assess the bio-effects
of right- and left-handed helical supramolecular assemblies by
circumventing enantiomeric effect of single molecules.
a) A. J. Boersma, B. L. Feringa, G. Roelfes, Angew. Chem. Int. Ed.
2009, 48, 3346-3348; b) F. Rodriguez-Llansola, B. Escuder, J. F.
Miravet, J. Am. Chem. Soc. 2009, 131, 11478-11484; c) D. Uraguchi, Y.
Ueki, T. Ooi, Science 2009, 326, 120-123; d) M. Hatano, T. Mizuno, A.
Izumiseki, R. Usami, T. Asai, M. Akakura, K. Ishihara, Angew. Chem.
Int. Ed. 2011, 50, 12189-12192; e) A.-B. Xia, D.-Q. Xu, C. Wu, L. Zhao,
Z.-Y. Xu, Chem. Eur. J. 2012, 18, 1055-1059.
[5]
(a) J. J. D. de Jong, L. N. Lucas, R. M. Kellogg, J. H. van Esch, B. L.
Feringa, Science 2004, 304, 278-281; b) M. J. Kim, S. J. Yoo, D. Y. Kim,
Adv. Funct. Mater.2006, 16, 2089-2094; c) P. Duan, Y. Li, L. Li, J. Deng,
M. Liu, J. Phys. Chem. B 2011, 115, 3322-3329; d) C. Gao, S. Silvi, X.
Ma, H. Tian, A. Credi, M. Venturi, Chem. Eur. J. 2012, 18, 16911-
16921; e) C. F. J. Faul, Acc. Chem. Res. 2014, 47, 3428-3438; f) R.
Wang, X. Li, J. Bai, J. Zhang, A. Liu, X. Wan, Macromolecules 2014, 47,
1553-1562.
[6]
[7]
a) G. Liang, Z. Yang, R. Zhang, L. Li, Y. Fan, Y. Kuang, Y. Gao, T.
Wang, W. W. Lu, B. Xu, Langmuir 2009, 25, 8419-8422; b) J. Li, Y.
Kuang, Y. Gao, X. Du, J. Shi, B. Xu, J. Am. Chem. Soc. 2013, 135,
542-545.
a)D. Hanein, B. Geiger, L. Addadi, Science 1994, 263, 1413-1416; b) R.
Bentley, Chem. Soc. Rev. 2005, 34, 609-624; c) T. Sun, D. Han, K.
Rhemann, L. Chi, H. Fuchs, J. Am. Chem. Soc. 2007, 129, 1496-1497;
d) K. Tang, H. Gan, Y. Li, L. Chi, T. Sun, H. Fuchs, J. Am. Chem. Soc.
2008, 130, 11284-11285; e) D. Bandyopadhyay, D. Prashar, Y.-Y. Luk,
Chem. Commun. 2011, 47, 6165-6167; f) X. Yao, Y. Hu, B. Cao, R.
Peng, J. Ding, Biomaterials 2013, 34, 9001-9009.
[8]
a) L. Brunsveld, H. Zhang, M. Glasbeek, J. A. J. M. Vekemans, E. W.
Meijer, J. Am. Chem. Soc. 2000, 122, 6175-6182; b) Y. Huang, J. Hu,
W. Kuang, Z. Wei, C. F. J. Faul, Chem. Commun. 2011, 47, 5554-5556;
c) Y. Li, B. Z. Li, Y. T. Fu, S. W. Lin, Y. G. Yang, Langmuir 2013, 29,
9721-9726; d) S. Manchineella, V. Prathyusha, U. D. Priyakumar, T.
Govindaraju, Chem. Eur. J. 2013, 19, 16615-16624; e) M. A. J.
Gillissen, M. M. E. Koenigs, J. J. H. Spiering, J. A. J. M. Vekemans, A.
R. A. Palmans, I. K. Voets, E. W. Meijer, J. Am. Chem. Soc. 2014, 136,
336-343; f) C. Liu, Q. Jin, K. Lv, L. Zhang, M. Liu, Chem. Commun.
2014, 50, 3702-3705.
Acknowledgements
This work was supported by the Innovation Program of
Shanghai
Municipal
Education
Commission
(201701070002E00061), the NSFC (51573092), and Program
for Professors of Special Appointment (Eastern Scholar) at the
Shanghai Institutions of Higher Learning.The authors thank
Ruibin Wang from the Instrumental Analysis Center of SJTU for
technical assistance during CD and VCD experiments.
[9]
a) H. Komori, Y. Inai, J. Org. Chem. 2007, 72, 4012-4022; b) M. M.
Smulders, I. A. Filot, J. M. Leenders, P. van der Schoot, A. R. Palmans,
A. P. Schenning, E. W. Meijer, J. Am. Chem. Soc. 2010, 132, 611-619;
c) A. Gopal, M. Hifsudheen, S. Furumi, M. Takeuchi, A. Ajayaghosh,
Angew. Chem. 2012, 124, 10657-10661; d) F. Aparicio, B. Nieto-Ortega,
F. Najera, F. J. Ramirez, J. T. L. Navarrete, J. Casado, L. Sanchez,
Angew. Chem. Int. Ed. 2014, 53, 1373-1377; e) J. Kumar, T.
Nakashima, T. Kawai, Langmuir 2014, 30, 6030-6037.
Keywords: Odd-even effect • Chirality inversion • Methylene
unit • Cell adhesion • supramolecular chemistry
[10] a) R. Iwaura, T. Shimizu, Angew. Chem. Int. Ed. 2006, 45, 4601-4604;
b) T. Muraoka, H. Cui, S. I. Stupp, J. Am. Chem. Soc. 2008, 130, 2946-
2947; c) J. Kim, J. Lee, W. Y. Kim, H. Kim, S. Lee, H. C. Lee, Y. S. Lee,
M. Seo, S. Y. Kim, Nat. Commun. 2015, 6, 6959-6966; d) D. P. Zhao, T.
van Leeuwen, J. L. Cheng, B. L. Feringa, Nat. Chem. 2017, 9, 250-256.
[11] a) Y. Yan, K. Deng, Z. Yu, Z. Wei, Angew. Chem. Int. Ed. 2009, 48,
2003-2006; b) E. T. Pashuck, S. I. Stupp, J. Am. Chem. Soc. 2010, 132,
8819-8821; c) S. Cantekin, D. W. R. Balkenende, M. M. J. Smulders, A.
R. A. Palmans, E. W. Meijer, Nat. Chem. 2011, 3, 42-46; d) Y. Fu, B. Li,
Z. Huang, Y. Li, Y. Yang, Langmuir 2013, 29, 6013-6017; e) Y. Nakano,
A. J. Markvoort, S. Cantekin, I. A. W. Filot, H. M. M. ten Eikelder, E. W.
Meijer, A. R. A. Palmans, J. Am. Chem. Soc. 2013, 135, 16497-16506;
f) H. G. Cui, A. G. Cheetham, E. T. Pashuck, S. I. Stupp, J. Am. Chem.
Soc. 2014, 136, 12461-12468.
[1]
a) A. Herbert, A. Rich, Genetica. 1999, 106, 37-47; b) A. Rich, S. Zhang,
Nat. Rev. Genet. 2003, 4, 566-572; c) R. D. Wells, Trends in
Biochemical Sciences 2007, 32, 271-278; d) A. Bacolla, R. D. Wells,
Mol. Carcinog. 2009, 48, 273-285; e) J. Zhao, A. Bacolla, G. Wang, K.
M. Vasquez, Cell. Mol. Life Sci. 2010, 67, 43-62; f) H. Toriumi,
Macromolecules 1984, 17, 1599-1605; g) S. Sasaki, H. Ogawa, S.
Kimura, Polym. J. 1991, 23, 1325-1331; h) Y. Inai, H. Komori, N.
Ousaka, Chem. Rec. 2007, 7, 191-202; i) M. D. Zotti, F. Formaggio, M.
Crisma, C. Peggion, A. Moretto, C. Toniolo, J. Pept. Sci. 2014, 20, 307-
322.
[2]
a) R. K. Das, O. F. Zouani, C. Labrugere, R. Oda, M.-C. Durrieu, Acs
Nano 2013, 7, 3351-3361; b) G. F. Liu, D. Zhang, C. L. Feng, Angew.
Chem. Int. Ed. 2014, 53, 7789-7793; c) K. Lv, L. Zhang, W. Lu, M. Liu,
ACS Appl. Mat. Interfaces 2014, 6, 18878-18884.
[12] a) H. Engelkamp, S. Middelbeek, R. J. M. Nolte, Science 1999, 284,
785-788; b) X. Zhu, P. Duan, L. Zhang, M. Liu, Chem. Eur. J. 2011, 17,
3429-3437; c) X. Wang, P. Duan, M. Liu, Chem. Commun. 2012, 48,
This article is protected by copyright. All rights reserved.

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7501-7503; d) R. Tamoto, N. Daugey, T. Buffeteau, B. Kauffmann, M.
Takafuji, H. Ihara, R. Oda, Chem. Commun .2015, 51, 3518-3521; e) M.
Deng, L. Zhang, Y. Jiang, M. Liu, Angew. Chem. Int. Ed. 2016, 55,
15062-15066; f) G. F. Liu, L. Y. Zhu, W. Ji, C. L. Feng, Z. X. Wei,
Angew. Chem. Int. Ed. 2016, 55, 2411-2415; g) G. F. Liu, J. Y. Liu, C. L.
Feng, Y. L. Zhao, Chem. Sci. 2017, 8, 1769-1775.
5825-5833; c) M.-O. M. Piepenbrock, G. O. Lloyd, N. Clarke, J. W.
Steed, Chem. Commun. 2008, 2644-2646; d) T. Y. Wang, Y. G. Li, M.
H. Liu, Soft Matter 2009, 5, 1066-1073; e) F. Aparicio, E. Matesanz, L.
Sanchez, Chem. Eur. J. 2014, 20, 14599-14603; f) P. Yadav, A.
Ballabh, New J. Chem. 2015, 39, 721-730.
[15] a) J. J. van Gorp, J. A. J. M. Vekemans, E. W. Meijer, J. Am. Chem.
Soc. 2002, 124, 14759-14769; b) Anuradha, D. D. La, M. Al Kobaisi, A.
Gupta, S. V. Bhosale, Chem. Eur. J. 2017, 23, 3950-3956.
[13] K. Toyoda, K. Miyamoto, N. Aoki, R. Morita, T. Omatsu, Nano Letters
2012, 12, 3645-3649.
[14] a) T. Shimizu, M. Masuda, J. Am. Chem. Soc. 1997, 119, 2812-2818;
b) T. Ishi-i, R. Iguchi, E. Snip, M. Ikeda, S. Shinkai, Langmuir 2001, 17,
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10.1002/anie.201801462
Angewandte Chemie International Edition
COMMUNICATION
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COMMUNICATION
The chirality inversion of
Jinying Liu, Feng Yuan, Xiaoyu
Ma, Dang-i Y. Auphedeous,
Changli Zhao, Chuntai Liu,
Changyu Shen and Chuanliang
Feng*
helical
nanofibers
is
triggered by odd−even effect
of methylene units from
homochiral L-phenylalanine
derivative during assembly.
Page No. – Page No.
The
results
show
an
increase in cell adhesion
and proliferation with left-
handed nanofibers whereas
The Cooperative Effect of both
Molecular and Supramolecular
Chirality on Cell Adhesion
weak
influence
was
observed with right-handed
nanofibers, even though
both were derived from L-
phenylalanine derivatives.
This article is protected by copyright. All rights reserved.