# How to achieve a successful biaxial marriage

Philippe Poulin

► To cite this version:

Philippe Poulin. How to achieve a successful biaxial marriage. Science, 2018, 360 (6390), pp.712-713.
10.1126/science.aat7399. hal-02337332

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Submitted on 3 May 2024

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# How to achieve a successful biaxial marriage

Philippe Poulin

► To cite this version:

Philippe Poulin. How to achieve a successful biaxial marriage. Science, 2018, 360 (6390), pp.712-713.
10.1126/science.aat7399. hal-02337332

HAL Id: hal-02337332

https://hal.science/hal-02337332v1

Submitted on 3 May 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>
MATERIALS SCIENCE

# How to achieve a successful biaxial marriage

## Coupling between organic and inorganic components results in a biaxial liquid crystal

By Philippe Poulin

Matter is generally divided into three states, namely solid, liquid, and gas. Liquid crystals form a fourth state of matter; they combine properties of liquids, such as fluidity and the ability to flow, with properties of crystalline solids, such as structural order and specific optical and electric properties. This unique combination makes liquid crystals valuable for numerous electro-optical applications, for example, in displays, cell phones, and televisions. They are also often found in living systems, for example in cell membranes made of phospholipids and in chromosomal DNA. On page 768 of this issue, Mundoor et al. (1) report a new class of liquid crystals made of long inorganic nanorods that are oriented in a perpendicular direction to the small organic molecules in which they are embedded.

Not all molecules or particles can reach the fourth state of matter. Liquid crystals are made of components—usually disks or rodlike molecules—that are anisotropic in shape. When the disks or rods are oriented along a single similar direction, but remain randomly positioned in space, they form

a nematic phase. The nematic phase can have high fluidity and is often viewed as the simplest liquid crystalline phase. It is of great technological importance, because most electro-optical applications are based on nematic liquid crystals.

The ordering of a nematic phase made solely of disks or rods can be specified by a single direction and therefore forms a uniaxial system. A more complex situation would occur if the building blocks were in the shape of, for example, a parallelepiped (see the figure). In this case, the material should form a biaxial phase, because the orientation of the boardlike molecules themselves can be specified by two axes. A biaxial nematic phase can in principle also be obtained by mixing disks and rods (see the figure). Biaxial nematics are expected to have useful properties, including fast switching speeds in potential electro-optical applications and to serve as models for studying fundamental questions about defects and topology.

Because of their expected properties and potential technological interest, biaxial nematic phases have been the topic of extensive research—and controversy—for several decades (2). Yet, their experimental realization remains challenging. Disks and

rods tend to phase separate, making it difficult or impossible to form biaxial phases by this approach. The use of boardlike molecules that adopt biaxial ordering has been the topic of controversies, with claims of biaxiality by some contradicted by others (2). The most encouraging results have been obtained with bent-core molecules and with some liquid-crystal polymers (2). The quest for biaxial nematics thus remains an open and exciting challenge.

Mundoor et al. report a strategy for making biaxial nematics that involves mixing inorganic nanorods and rodlike organic molecules. This approach differs from previous studies, which typically used mixtures of particles with different shapes or molecules with complex structures. In contrast, the particles in the authors' mixture have the same simple shape, but differ in size. The rodlike organic molecules are about 2 nm long, whereas the inorganic nanorods are about 1 µm (1000 nm) in length. On their own, the nanorods and the rodlike molecules can form uniaxial nematics. By controlling the chemistry of the nanorods, Mundoor et al. achieve their homogeneous dispersion and stabilization in the liquid crystal made of the rodlike organic molecules. In a well-defined concentration regime, the orientation of the nanorods is spontaneously orthogonal to that of the organic molecules (see the figure). This mixture thus forms a biaxial nematic liquid crystal.

The beauty of this achievement lies in the delicate control of the interactions between the nanorods and the organic molecules. If the interactions between them are too weak, the orientation of the nanorods and of the molecules would not be correlated. If the interactions are too strong, they would phase-separate and form other structures (3). By finely controlling the chemistry of the nanorods, Mundoor et al. have found the right balance to achieve a well-organized coupling of the inorganic and organic components. Because of this coupling, the nanorods disturb the ordering of the small molecules slightly, thereby making the liquid crystal state a bit less stable when heated. Thus, the small mol-

Centre de Recherche Paul Pascal - CNRS, University of Bordeaux, Avenue Schweitzer, 33600 Pessac, France.
Email: poulin@crpp-bordeaux.cnrs.fr

## How to make a biaxial nematic

Previous efforts to make biaxial nematics with either boardlike molecules or component mixtures have had limited success. Mundoor et al. used a different strategy to create a biaxial nematic by tuning the interactions between long inorganic nanorods and short organic molecules.

<figure><img src="image_2.png" /><figcaption>**Boardlike molecules**</figcaption></figure>

Whether these molecules can adopt biaxial ordering remains controversial.

<figure><img src="image_3.png" /><figcaption>**Disk- and rodlike components**</figcaption></figure>

Mixtures of similarly sized disk- and rod-shaped molecules tend to phase separate.

<figure><img src="image_4.png" /><figcaption>**Hybrid mixture**</figcaption></figure>

Weak coupling between different components results in biaxial ordering.
## MATERIALS SCIENCE

# How to achieve a successful biaxial marriage

Coupling between organic and inorganic components results in a biaxial liquid crystal

By Philippe Poulin

Matter is generally divided into three states, namely solid, liquid, and gas. Liquid crystals form a fourth state of matter; they combine properties of liquids, such as fluidity and the ability to flow, with properties of crystalline solids, such as structural order and specific optical and electric properties. This unique combination makes liquid crystals valuable for numerous electro-optical applications, for example, in displays, cell phones, and televisions. They are also often found in living systems, for example in cell membranes made of phospholipids and in chromosomal DNA. On page 768 of this issue, Mundoor et al. (1) report a new class of liquid crystals made of long inorganic nanorods that are oriented in a perpendicular direction to the small organic molecules in which they are embedded.

Not all molecules or particles can reach the fourth state of matter. Liquid crystals are made of components—usually disks or rodlike molecules—that are anisotropic in shape. When the disks or rods are oriented along a single similar direction, but remain randomly positioned in space, they form

a nematic phase. The nematic phase can have high fluidity and is often viewed as the simplest liquid crystalline phase. It is of great technological importance, because most electro-optical applications are based on nematic liquid crystals.

The ordering of a nematic phase made solely of disks or rods can be specified by a single direction and therefore forms a uniaxial system. A more complex situation would occur if the building blocks were in the shape of, for example, a parallelepiped (see the figure). In this case, the material should form a biaxial phase, because the orientation of the boardlike molecules themselves can be specified by two axes. A biaxial nematic phase can in principle also be obtained by mixing disks and rods (see the figure). Biaxial nematics are expected to have useful properties, including fast switching speeds in potential electro-optical applications and to serve as models for studying fundamental questions about defects and topology.

Because of their expected properties and potential technological interest, biaxial nematic phases have been the topic of extensive research—and controversy—for several decades (2). Yet, their experimental realization remains challenging. Disks and

rods tend to phase separate, making it difficult or impossible to form biaxial phases by this approach. The use of boardlike molecules that adopt biaxial ordering has been the topic of controversies, with claims of biaxiality by some contradicted by others (2). The most encouraging results have been obtained with bent-core molecules and with some liquid-crystal polymers (2). The quest for biaxial nematics thus remains an open and exciting challenge.

Mundoor et al. report a strategy for making biaxial nematics that involves mixing inorganic nanorods and rodlike organic molecules. This approach differs from previous studies, which typically used mixtures of particles with different shapes or molecules with complex structures. In contrast, the particles in the authors' mixture have the same simple shape, but differ in size. The rodlike organic molecules are about 2 nm long, whereas the inorganic nanorods are about 1 µm (1000 nm) in length. On their own, the nanorods and the rodlike molecules can form uniaxial nematics. By controlling the chemistry of the nanorods, Mundoor et al. achieve their homogeneous dispersion and stabilization in the liquid crystal made of the rodlike organic molecules. In a well-defined concentration regime, the orientation of the nanorods is spontaneously orthogonal to that of the organic molecules (see the figure). This mixture thus forms a biaxial nematic liquid crystal.

The beauty of this achievement lies in the delicate control of the interactions between the nanorods and the organic molecules. If the interactions between them are too weak, the orientation of the nanorods and of the molecules would not be correlated. If the interactions are too strong, they would phase-separate and form other structures (3). By finely controlling the chemistry of the nanorods, Mundoor et al. have found the right balance to achieve a well-organized coupling of the inorganic and organic components. Because of this coupling, the nanorods disturb the ordering of the small molecules slightly, thereby making the liquid crystal state a bit less stable when heated. Thus, the small mol-

Centre de Recherche Paul Pascal - CNRS, University of Bordeaux, Avenue Schweitzer, 33600 Pessac, France.
Email: poulin@crpp-bordeaux.cnrs.fr

## How to make a biaxial nematic

Previous efforts to make biaxial nematics with either boardlike molecules or component mixtures have had limited success. Mundoor et al. used a different strategy to create a biaxial nematic by tuning the interactions between long inorganic nanorods and short organic molecules.

<figure><img src="image_2.png" /><figcaption>**Boardlike molecules**</figcaption></figure>

Whether these molecules can adopt biaxial ordering remains controversial.

<figure><img src="image_3.png" /><figcaption>**Disk- and rodlike components**</figcaption></figure>

Mixtures of similarly sized disk- and rod-shaped molecules tend to phase separate.

<figure><img src="image_4.png" /><figcaption>**Hybrid mixture**</figcaption></figure>

Weak coupling between different components results in biaxial ordering.
ecules must be cooled down a bit more to
induce their transition from the isotropic
to the nematic phase (4).

The authors convincingly characterize
the materials with several optical methods.
The results show that the biaxial nematic
is not a simple superposition of two uni-
axial nematics. Anisotropic interactions
induce a biaxial orientation distribution of
the nanorods, which in turn induce biaxil-
ity in the distribution of the organic mol-
ecules. Thus, the properties of the hybrid
materials are even richer than would be
expected from a simple superposition of
uniaxial nematics. Furthermore, the pres-
ent approach allows the use of organic
liquid crystals with rather simple organic
molecules, making it easier to control their
stability and their temperature transitions
and to make them suitable for applica-
tions. It would be more difficult to control
and tune the thermodynamic properties
of molecules and polymers with complex
structures such as those that have been
used in the past to make biaxial nematics.

"The beauty of this achievement lies in the delicate control of the interactions between the nanorods and the organic molecules [in the biaxial liquid crystal]."

Mundoor et al.'s study opens the door
for a range of novel nematic liquid crystals.
As demonstrated by the authors, the key is
to achieve moderate coupling between the
inorganic inclusions and the organic host.
Tuning this coupling could lead to other
states; following simple theoretical expecta-
tions (4), it may be possible to expect coex-
istence of nematic phases and even critical
phase transitions. Use of other shapes, such
as disks, boards, and chiral species, could
further enrich this class of hybrid materi-
als. The optical properties and response to
external fields of these hybrid may form
the basis for future applications in which
the functionalities of organic and inorganic
materials are combined.

REFERENCES

1. H. Mundoor et al., *Science* **360**, 768 (2018).

2. C. Tschierske, D. J. Photinos, *J. Mater. Chem.* **20**, 4263 (2010).

3. I. Mušević, *Materials* **11**, 24 (2018).

4. P. Poulin, V. Raghunathan, P. Richetti, D. Roux, *J. Phys. II France* **4**, 1557 (1994).

10.1126/science.aat7399

TRANSCRIPTION

BRD4 and MYC—clarifying
regulatory specificity

A study dissects the primary function of cancer-associated
transcription factors

By Arianna Sabò and Bruno Amati

The transcriptional output of cells is governed by the interplay among sequence-specific transcription factors (TFs), epigenetic DNA and chromatin modifications, and their writers, readers, and erasers, along with the basal transcriptional machinery and RNA polymerase II (Pol2). Assessing the contribution of individual factors to specific transcriptional programs is an essential albeit elusive goal, as exemplified by studies of the chromatin-associated factor BRD4 (a BET family member) (1) or the oncogenic TF MYC (2). BET proteins interact with acetylated histones in active regulatory domains (promoters and enhancers) and promote Pol2 activity. Despite the general nature of this mechanism, BET inhibitors (BETis) have shown selective effects on gene expression—in particular, suppression of *MYC* and other oncogenes in tumor cells (1). MYC is a sequence-specific DNA-binding protein that has been proposed to function either as a selective regulator (2–4) or as a general activator (“amplifier”) of transcriptional activity (5, 6). Determining regulatory specificities is hampered by the need to identify productive DNA-binding events and to distinguish direct from indirect transcriptional responses. On page 800 of this issue, Muhar *et al.* (7) provide unprecedented resolution on the regulatory roles of MYC and BRD4, improving our understanding of these cancer-associated TFs.

The authors induced acute degradation of endogenous BRD4 or MYC in two cancer cell lines and profiled immediate transcriptional changes (see the figure). Inducing BRD4 degradation reduced the elongating form of Pol2 and globally down-regulated transcription, pointing to BRD4—rather than the whole BET family (8)—as a general coactivator of Pol2. Treatment of cells with the BETi JQ1 led to different outcomes, depending on the dosage: Whereas high doses suppressed all transcription, mimicking BRD4 degradation, lower doses—albeit still toxic to cancer cells—had more limited consequences, pos-

sibly because of a dose-dependent removal
of BRD4 from chromatin (9). Such selective
transcriptional responses to BETis have been
the basis of their development as antican-
cer drugs because oncogenes—particularly
MYC—were generally more sensitive than
housekeeping genes to BET inhibition (1).
Thus, understanding the molecular features
that determine differential sensitivity to
BETis is of crucial importance.

Neither the level of BRD4 binding to
promoters (7, 10, 11) nor the presence of su-
perenhancers (7, 11, 12) were sufficient to
predict the sensitivity of a gene to JQ1. Al-
though selectivity could also be due to the
differential ability of promoters to undergo
compensatory increases in Pol2 loading (11),
data mining in genome binding profiles al-
lowed Muhar et al. to identify other TFs and
cofactors with predictive power, albeit not in
a general manner; indeed, these factors were
enriched on different subsets of JQ1-sensitive
genes. Therefore, besides acetylated histones,
other proteins may mediate BRD4 recruit-
ment and/or activity on chromatin, contrib-
uting to the selective effects of BETis.

Of note, the global impairment of Pol2
elongation upon BRD4 degradation occurred
without displacement of the elongation fac-
tor cyclin-dependent kinase 9 (CDK9), and
BET and CDK9 inhibitors affected distinct
groups of genes (7, 8). Thus, besides recruit-
ing CDK9, BRD4 may directly regulate Pol2
activity, possibly through intrinsic acetyl-
transferase and/or kinase activities (I).

The enhanced sensitivity of tumor cells
to JQ1 is determined at least in part by its
inhibitory action on MYC expression and/
or activity. Thus, Muhar *et al.* addressed the
consequences of acute MYC degradation in
cancer cells, revealing a fundamentally differ-
ent scenario from that observed with BRD4.

In recent years, the selectivity of MYC as a
transcriptional regulator has been the subject
of intense debate (2-6). In the work discussed
here, only a few hundred genes showed de-
creased messenger RNA output upon loss of
MYC, a large majority of the transcriptome
remaining unaffected (7). Important insight
was provided by the identity of MYC-depen-
dent genes, which are involved in protein and
nucleic acid biosynthetic pathways, among

Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Email: bruno.amati@ieo.it
ecules must be cooled down a bit more to
induce their transition from the isotropic
to the nematic phase (4).

The authors convincingly characterize
the materials with several optical methods.
The results show that the biaxial nematic
is not a simple superposition of two uni-
axial nematics. Anisotropic interactions
induce a biaxial orientation distribution of
the nanorods, which in turn induce biaxil-
ity in the distribution of the organic mol-
ecules. Thus, the properties of the hybrid
materials are even richer than would be
expected from a simple superposition of
uniaxial nematics. Furthermore, the pres-
ent approach allows the use of organic
liquid crystals with rather simple organic
molecules, making it easier to control their
stability and their temperature transitions
and to make them suitable for applica-
tions. It would be more difficult to control
and tune the thermodynamic properties
of molecules and polymers with complex
structures such as those that have been
used in the past to make biaxial nematics.

"The beauty of this achievement lies in the delicate control of the interactions between the nanorods and the organic molecules [in the biaxial liquid crystal]."

Mundoor et al.'s study opens the door
for a range of novel nematic liquid crystals.
As demonstrated by the authors, the key is
to achieve moderate coupling between the
inorganic inclusions and the organic host.
Tuning this coupling could lead to other
states; following simple theoretical expecta-
tions (4), it may be possible to expect coex-
istence of nematic phases and even critical
phase transitions. Use of other shapes, such
as disks, boards, and chiral species, could
further enrich this class of hybrid materi-
als. The optical properties and response to
external fields of these hybrid may form
the basis for future applications in which
the functionalities of organic and inorganic
materials are combined.

REFERENCES

1. H. Mundoor et al., *Science* **360**, 768 (2018).

2. C. Tschierske, D. J. Photinos, *J. Mater. Chem.* **20**, 4263 (2010).

3. I. Mušević, *Materials* **11**, 24 (2018).

4. P. Poulin, V. Raghunathan, P. Richetti, D. Roux, *J. Phys. II France* **4**, 1557 (1994).

10.1126/science.aat7399

TRANSCRIPTION

BRD4 and MYC—clarifying
regulatory specificity

A study dissects the primary function of cancer-associated
transcription factors

By Arianna Sabò and Bruno Amati

The transcriptional output of cells is governed by the interplay among sequence-specific transcription factors (TFs), epigenetic DNA and chromatin modifications, and their writers, readers, and erasers, along with the basal transcriptional machinery and RNA polymerase II (Pol2). Assessing the contribution of individual factors to specific transcriptional programs is an essential albeit elusive goal, as exemplified by studies of the chromatin-associated factor BRD4 (a BET family member) (1) or the oncogenic TF MYC (2). BET proteins interact with acetylated histones in active regulatory domains (promoters and enhancers) and promote Pol2 activity. Despite the general nature of this mechanism, BET inhibitors (BETis) have shown selective effects on gene expression—in particular, suppression of *MYC* and other oncogenes in tumor cells (1). MYC is a sequence-specific DNA-binding protein that has been proposed to function either as a selective regulator (2–4) or as a general activator (“amplifier”) of transcriptional activity (5, 6). Determining regulatory specificities is hampered by the need to identify productive DNA-binding events and to distinguish direct from indirect transcriptional responses. On page 800 of this issue, Muhar *et al.* (7) provide unprecedented resolution on the regulatory roles of MYC and BRD4, improving our understanding of these cancer-associated TFs.

The authors induced acute degradation of endogenous BRD4 or MYC in two cancer cell lines and profiled immediate transcriptional changes (see the figure). Inducing BRD4 degradation reduced the elongating form of Pol2 and globally down-regulated transcription, pointing to BRD4—rather than the whole BET family (8)—as a general coactivator of Pol2. Treatment of cells with the BETi JQ1 led to different outcomes, depending on the dosage: Whereas high doses suppressed all transcription, mimicking BRD4 degradation, lower doses—albeit still toxic to cancer cells—had more limited consequences, pos-

sibly because of a dose-dependent removal
of BRD4 from chromatin (9). Such selective
transcriptional responses to BETis have been
the basis of their development as antican-
cer drugs because oncogenes—particularly
MYC—were generally more sensitive than
housekeeping genes to BET inhibition (1).
Thus, understanding the molecular features
that determine differential sensitivity to
BETis is of crucial importance.

Neither the level of BRD4 binding to
promoters (7, 10, 11) nor the presence of su-
perenhancers (7, 11, 12) were sufficient to
predict the sensitivity of a gene to JQ1. Al-
though selectivity could also be due to the
differential ability of promoters to undergo
compensatory increases in Pol2 loading (11),
data mining in genome binding profiles al-
lowed Muhar et al. to identify other TFs and
cofactors with predictive power, albeit not in
a general manner; indeed, these factors were
enriched on different subsets of JQ1-sensitive
genes. Therefore, besides acetylated histones,
other proteins may mediate BRD4 recrut-
ment and/or activity on chromatin, contrib-
uting to the selective effects of BETis.

Of note, the global impairment of Pol2
elongation upon BRD4 degradation occurred
without displacement of the elongation fac-
tor cyclin-dependent kinase 9 (CDK9), and
BET and CDK9 inhibitors affected distinct
groups of genes (7, 8). Thus, besides recruit-
ing CDK9, BRD4 may directly regulate Pol2
activity, possibly through intrinsic acetyl-
transferase and/or kinase activities (I).

The enhanced sensitivity of tumor cells
to JQ1 is determined at least in part by its
inhibitory action on MYC expression and/
or activity. Thus, Muhar *et al.* addressed the
consequences of acute MYC degradation in
cancer cells, revealing a fundamentally differ-
ent scenario from that observed with BRD4.

In recent years, the selectivity of MYC as a
transcriptional regulator has been the subject
of intense debate (2-6). In the work discussed
here, only a few hundred genes showed de-
creased messenger RNA output upon loss of
MYC, a large majority of the transcriptome
remaining unaffected (7). Important insight
was provided by the identity of MYC-depen-
dent genes, which are involved in protein and
nucleic acid biosynthetic pathways, among

Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Email: bruno.amati@ieo.it
Science

# How to achieve a successful biaxial marriage

Philippe Poulin

Science **360** (6390), 712-713.

DOI: 10.1126/science.aat7399

**ARTICLE TOOLS** http://science.sciencemag.org/content/360/6390/712

**RELATED CONTENT** http://science.sciencemag.org/content/sci/360/6390/768.full

**REFERENCES** This article cites 4 articles, 1 of which you can access for free
http://science.sciencemag.org/content/360/6390/712#BIBL

**PERMISSIONS** http://www.sciencemag.org/help/reprints-and-permissions
Science

How to achieve a successful biaxial marriage

Philippe Poulin

Science **360** (6390), 712-713.

DOI: 10.1126/science.aat7399

**ARTICLE TOOLS** http://science.sciencemag.org/content/360/6390/712

**RELATED CONTENT** http://science.sciencemag.org/content/sci/360/6390/768.full

**REFERENCES** This article cites 4 articles, 1 of which you can access for free
http://science.sciencemag.org/content/360/6390/712#BIBL

**PERMISSIONS** http://www.sciencemag.org/help/reprints-and-permissions

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