Proteins associated with the regulation of organ size and shape have been found to respond to the mechanics of the microenvironment in ways that specifically affect the decision of adult cardiac stem cells to generate muscular or vascular cells.
Cell development for specific functions — so-called cell differentiation — is crucial for maintaining healthy tissue and organs. Two proteins in particular — the Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1 or TAZ) — have been linked with control of cell differentiation in the tissues of the lymphatic, circulatory, intestinal and neural systems, as well as regulating embryonic stem cell renewal.
An international collaboration of researchers has now identified that changes in the elasticity and nanotopography of the cellular environment of these proteins can affect how heart stem cells differentiate with implications for the onset of heart diseases.
Researchers at the International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS) collaborated with researchers in Finland, Italy, the Netherlands, Saudi Arabia and the Czech Republic in the study.
They engineered YAP and TAZ proteins that expressed green fluorescent protein so that their location within the cell could be tracked. They then prepared cell substrates from smart biomaterials displaying dynamic control of elasticity and nanostructure with temperature.
“Our data provide the first evidence for YAP/TAZ shuttling activity between the nucleus and the cytoplasm being promptly activated in response to dynamic modifications in substrate stiffness or nanostructure,” explain the researchers.
Observations of gene expression highlighted the key role of YAP/TAZ proteins in cell differentiation. In further investigations on the effect of substrate stiffness they also found that cell differentiation was most efficient for substrates displaying stiffness similar to that found in the heart.
The authors suggest that understanding the effects of microenvironment nanostructure and mechanics on how these proteins affect cell differentiation could be used to aid processes that maintain a healthy heart.
They conclude, “These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design.”
International Center of Materials Nanoarchitectonics (MANA)
National Institute for Materials Science
1-1 Namiki Tsukuba, Ibaraki 305-0044 JAPAN
International Center for Materials Nanoarchitectonics (WPI-MANA)
Address: 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure. Diogo Mosqueira,1,2,† Stefania Pagliari,1,3,† Koichiro Uto,1 Mitsuhiro Ebara,1 Sara Romanazzo,1 Carmen Escobedo-Lucea,4 Jun Nakanishi,1 Akiyoshi Taniguchi,1 Ornella Franzese,5 Paolo Di Nardo,6 Marie Jose´ Goumans,7 Enrico Traversa,8 Perpetua Pinto-do-O,2 Takao Aoyagi,1,‡,* and Giancarlo Forte1,9,†,0* 2014 ACS NANO; DOI: 10.1021/nn4058984.
1. Biomaterials Unit, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan
2. Instituto de Engenharia Biomedica-INEB, Universidade do Porto, Porto, Portugal
3. Japan Society for the Promotion of Science (JSPS), Tokyo, Japan
4. Academy of Finland Research Fellow, Division of Pharmaceutical Biosciences/Center for Drug Research (CDR), University of Helsinki, Helsinki, Finland
5. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
6. Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy
7. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
8. King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
9. International Clinical Research Center (ICRC), Integrated Center of Cellular Therapy and Regenerative Medicine, St. Anne's University Hospital, Brno, Czech Republic.
0. Present address: International Clinical Research Center (ICRC), Integrated Center of Cellular Therapy and Regenerative Medicine, St. Anne's University Hospital, Brno, Czech Republic.
†These authors contributed equally.
‡These authors contributed equally.
* Corresponding authors
New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia
New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences