EFFECTS OF SUBSTRATE MECHANICS AND NANOTOPOGRAPHY ON HUMAN MESENCHYMAL STEM CELLS MECHANOSOME

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F18%3A00070387" target="_blank" >RIV/00159816:_____/18:00070387 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

EFFECTS OF SUBSTRATE MECHANICS AND NANOTOPOGRAPHY ON HUMAN MESENCHYMAL STEM CELLS MECHANOSOME

Popis výsledku v původním jazyce

The ability of cells to perceive the mechanics and nanostructure of the extracellular matrix (ECM) relies on the activity of a number of intracellular proteins, collectively defined as mechanosome. By modifying the expression, the interaction or the localization of such proteins, the cell dynamically responds to modifications in ECM compliance and nanotopography by activating specific genetic programs. Among the intracellular proteins acting as mechanosensors, those composing the Focal Adhesions (FAs) and the effectors of Hippo pathway YAP/TAZ have been recently described as the main actors. Here, while confirming that both FAs and YAP/TAZ respond to substrate mechanics, we demonstrate that they are sensitive to dynamic modifications of substrate nanotopography by rearranging their structure or their localization. We also show that they are not sensitive to cell polarity when cell area is kept constant. In particular, the assembly of FAs, measured by image analysis through vinculin spike formation at the periphery of the cell, and YAP/TAZ nuclear shuttling to and from the cell nucleus, are proven to be sensitive to the changes in ECM nanostructure as mimicked by thermoresponsive polymers based on crosslinked poly-caprolactone (PCL). By using such a tool, we show that YAP nuclear presence -and thus its transcriptional activity - is promptly impaired by dynamic changes in substrate nanopattern. The same dynamic modifications alter FA size distribution, thus suggesting a change in their molecular composition. In doing so, we show at single cell level that the inhibition of cell spreading and of its ability to perceive ECM mechanics by either micropatterned surfaces or pharmacological inhibitors of RhoA/ROCK or Myosin IIa pathways results in the depletion of YAP/TAZ nuclear activity, the impairment of FAs formation and the regulation of genes involved in cell-matrix interaction. Altogether our results expand the current understanding of cell mechanosensing apparatus and directly connect YAP/TAZ transcriptional activity to the ability of the cell to feel the dynamic modifications of ECM composition.

Název v anglickém jazyce

EFFECTS OF SUBSTRATE MECHANICS AND NANOTOPOGRAPHY ON HUMAN MESENCHYMAL STEM CELLS MECHANOSOME

Popis výsledku anglicky

The ability of cells to perceive the mechanics and nanostructure of the extracellular matrix (ECM) relies on the activity of a number of intracellular proteins, collectively defined as mechanosome. By modifying the expression, the interaction or the localization of such proteins, the cell dynamically responds to modifications in ECM compliance and nanotopography by activating specific genetic programs. Among the intracellular proteins acting as mechanosensors, those composing the Focal Adhesions (FAs) and the effectors of Hippo pathway YAP/TAZ have been recently described as the main actors. Here, while confirming that both FAs and YAP/TAZ respond to substrate mechanics, we demonstrate that they are sensitive to dynamic modifications of substrate nanotopography by rearranging their structure or their localization. We also show that they are not sensitive to cell polarity when cell area is kept constant. In particular, the assembly of FAs, measured by image analysis through vinculin spike formation at the periphery of the cell, and YAP/TAZ nuclear shuttling to and from the cell nucleus, are proven to be sensitive to the changes in ECM nanostructure as mimicked by thermoresponsive polymers based on crosslinked poly-caprolactone (PCL). By using such a tool, we show that YAP nuclear presence -and thus its transcriptional activity - is promptly impaired by dynamic changes in substrate nanopattern. The same dynamic modifications alter FA size distribution, thus suggesting a change in their molecular composition. In doing so, we show at single cell level that the inhibition of cell spreading and of its ability to perceive ECM mechanics by either micropatterned surfaces or pharmacological inhibitors of RhoA/ROCK or Myosin IIa pathways results in the depletion of YAP/TAZ nuclear activity, the impairment of FAs formation and the regulation of genes involved in cell-matrix interaction. Altogether our results expand the current understanding of cell mechanosensing apparatus and directly connect YAP/TAZ transcriptional activity to the ability of the cell to feel the dynamic modifications of ECM composition.

Druh

D - Stať ve sborníku

CEP obor

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OECD FORD obor

21000 - Nano-technology

Projekt

<a href="/cs/project/LQ1605" target="_blank" >LQ1605: Translační medicína</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

9TH INTERNATIONAL CONFERENCE ON NANOMATERIALS - RESEARCH &amp; APPLICATION (NANOCON 2017)

ISBN

978-80-87294-81-9

ISSN

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e-ISSN

neuvedeno

Počet stran výsledku

6

Strana od-do

611-616

Název nakladatele

TANGER LTD

Místo vydání

SLEZSKA

Místo konání akce

Brno

Datum konání akce

18. 10. 2017

Typ akce podle státní příslušnosti

EUR - Evropská akce

Kód UT WoS článku

000452823300101