MECHANOSENSING PROTEINS YAP/TAZ DYNAMICALLY CONTROL CARDIAC CELL MATURATION AND FUNCTION BY SENSING ECM NANOTOPOGRAPHY

1 Pagliari Stefania
Co-authors:
1 Vinarsky Vladimir 1 Perestrelo Ana Rubina 1 Martino Fabiana 1 Oliver De La Cruz Jorge 1 Forte Giancarlo
Institution:
1 CTM – Center for Translational Medicine, International Clinical Research Center (ICRC), St. Anne’s University Hospital, Brno, Czech Republic, EU
Conference:
8th International Conference on Nanomaterials - Research & Application, Hotel Voronez I, Brno, Czech Republic, EU, October 19th - 21st 2016
Proceedings:
Proceedings 8th International Conference on Nanomaterials - Research & Application
Pages:
419-423
ISBN:
978-80-87294-71-0
ISSN:
2694-930X
Published:
17th March 2017
Proceedings of the conference were published in Web of Science and Scopus.
Metrics:
34 views / 5 downloads
Abstract

The composition and arrangement of extracellular matrix (ECM) components in adult cardiac tissue plays a key role in the organization and alignment of synchronously and functionally beating cardiomyocytes. Following Heart failure (HF) - the end stage of cardiac pathologies in which cardiac muscle is not able to pump adequate blood to the organism – critical changes in mechanics and nanotopography occur along with the composition of cardiac ECM. Such modifications in ECM compliance and nanotopography – collectively defined as remodelling - are deemed to hinder local cell viability and function. At the moment, reliable in vitro models of the dynamic modifications occurring in vivo during cardiac remodelling process are missing. The Mechanosensing pathway Hippo acts through its effectors YAP/TAZ and is sensitive to changes in ECM mechanical properties. In the present study we demonstrate that, while being responsive to substrate compliance in a pathophysiological range (0,3-40 kPa), the nuclear localization and transcriptional activity of YAP/TAZ can be tuned by dynamical modifications of surface mechanics and nanotopography, as demonstrated by ad hoc developed thermo-responsive polymers displaying shape-memory properties.

Keywords: Cardiac progenitor cells, mechanobiology, thermo-responsive polymers, Hippo pathway
Scroll to Top