# Fileset

[[Vol. 12]Heart cells respond to stiff environments_ WPI-MANA.pdf](https://mdr.nims.go.jp/filesets/34556c79-83de-4ff8-bc89-dc8da950621b/download)

## Creator

International Center for Materials Nanoarchitectonics (WPI-MANA)

## Rights

In Copyright[In Copyright](http://rightsstatements.org/vocab/InC/1.0/)

## Other metadata

[[Research Highlights Vol.12] Heart cells respond to stiff environments ](https://mdr.nims.go.jp/datasets/47eaa2da-0565-424f-abb9-baa5cfc87a5d)

## Fulltext

2022/04/04 10:23 Heart cells respond to stiff environments| MANAhttps://www.nims.go.jp/mana/research/highlights/vol12.html 1/2Previous  Index  NextResearch Highlights[Vol. 12]Heart cells respond to stiff environments14 Mar, 2014Proteins associated with the regulation of organ size and shape have beenfound to respond to the mechanics of the microenvironment in ways thatspecifically affect the decision of adult cardiac stem cells to generatemuscular or vascular cells.Figure : Schematic illustrating how mechanical properties of substrates affectwhere YAP/TAZ protein localization in cardiac stem cells (left) and how thisaffects stem cell development and function (right).Cell development for specific functions — so-called cell differentiation — is crucial for maintaininghealthy tissue and organs. Two proteins in particular — the Yes-associated protein (YAP) and WWdomain-containing transcription regulator protein 1 (WWTR1 or TAZ) — have been linked withcontrol of cell differentiation in the tissues of the lymphatic, circulatory, intestinal and neuralsystems, as well as regulating embryonic stem cell renewal. An international collaboration ofresearchers has now identified that changes in the elasticity and nanotopography of the cellularenvironment of these proteins can affect how heart stem cells differentiate with implications for theonset of heart diseases.Researchers at the International Center for Materials Nanoarchitectonics (MANA), National Institutefor Materials Science (NIMS) collaborated with researchers in Finland, Italy, the Netherlands, SaudiArabia and the Czech Republic in the study.They engineered YAP and TAZ proteins that expressed green fluorescent protein so that theirlocation within the cell could be tracked. They then prepared cell substrates from smartbiomaterials displaying dynamic control of elasticity and nanostructure with temperature. “Ourdata provide the first evidence for YAP/TAZ shuttling activity between the nucleus and thehttps://www.nims.go.jp/mana/research/highlights/vol11.htmlhttps://www.nims.go.jp/mana/research/highlights/index.htmlhttps://www.nims.go.jp/mana/research/highlights/vol13.html2022/04/04 10:23 Heart cells respond to stiff environments| MANAhttps://www.nims.go.jp/mana/research/highlights/vol12.html 2/2cytoplasm being promptly activated in response to dynamic modifications in substrate stiffness ornanostructure,” 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 differentiationwas most efficient for substrates displaying stiffness similar to that found in the heart.The authors suggest that understanding the effects of microenvironment nanostructure andmechanics on how these proteins affect cell differentiation could be used to aid processes thatmaintain a healthy heart. They conclude, “These proteins are indicated as potential targets tocontrol cardiac progenitor cell fate by materials design.”Reference"Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors ofsubstrate mechanics and nanostructure"Diogo Mosqueira, Stefania Pagliari, Koichiro Uto, Mitsuhiro Ebara, Sara Romanazzo, CarmenEscobedo-Lucea, Jun Nakanishi, Akiyoshi Taniguchi, Ornella Franzese, Paolo Di Nardo, Marie JoséGoumans, Enrico Traversa, Perpetua Pinto-do-Ó, Takao Aoyagi, and Giancarlo ForteJournal : ACS NANO 8, 3, 2033–2047, (2014).DOI : 10.1021/nn4058984Contact informationInternational Center for Materials Nanoarchitectonics(WPI-MANA)National Institute for Materials Science1-1 Namiki, Tsukuba, Ibaraki 305-0044 JapanPhone: +81-29-860-4710E-mail: mana-pr[AT]ml.nims.go.jphttps://pubs.acs.org/doi/abs/10.1021/nn4058984