Freeley, Mark

Gadegaard, Nikolaj

Gondarenko, Sasha

Hawkes, William

Hone, James

Hu, Junquiang

Huang, Da

Iskratsch, Thomas

Marhuenda, Emilie

O'Neill, Caoimhe

Palma, Matteo

Pandey, Pragati

Reynolds, Paul

Wilson, Darren Graham Samuel

The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. Changing collagen expression and cross-linking regulate the rigidity of the cardiac extracellular matrix (ECM). Additionally, basal lamina glycoproteins, especially laminin and fibronectin regulate cardiomyocyte adhesion formation, mechanics and mechanosignalling. Laminin is abundant in the healthy heart, but fibronectin is increasingly expressed in the fibrotic heart. ECM receptors are co-regulated with the changing ECM. Owing to differences in integrin dynamics, clustering and downstream adhesion formation this is expected to ultimately influence cardiomyocyte mechanosignalling; however, details remain elusive. Here, we sought to investigate how different cardiomyocyte integrin/ligand combinations affect adhesion formation, traction forces and mechanosignalling, using a combination of uniformly coated surfaces with defined stiffness, polydimethylsiloxane nanopillars, micropatterning and specifically designed bionanoarrays for precise ligand presentation. Thereby we found that the adhesion nanoscale organization, signalling and traction force generation of neonatal rat cardiomyocytes (which express both laminin and fibronectin binding integrins) are strongly dependent on the integrin/ligand combination. Together our data indicate that the presence of fibronectin in combination with the enhanced stiffness in fibrotic areas will strongly impact on the cardiomyocyte behaviour and influence disease progression

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Regulation of cardiomyocyte adhesion and mechanosignalling through distinct nanoscale behaviour of integrin ligands mimicking healthy or fibrotic extracellular matrix

http://eprints.gla.ac.uk/269473/1/269473.pdf

Regulation of cardiomyocyte adhesion and mechanosignalling through distinct nanoscale behaviour of integrin ligands mimicking healthy or fibrotic ECM

Regulation of cardiomyocyte adhesion and mechanosignalling through distinct nanoscale behaviour of integrin ligands mimicking healthy or fibrotic ECM

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