Mechanoradicals in tensed tendon collagen as a source of oxidative stress

Christopher Zapp, Agnieszka Obarska-Kosinska, Benedikt Rennekamp, Markus Kurth, David M. Hudson, Davide Mercadante, Uladzimir Barayeu, Tobias P. Dick, Vasyl Denysenkov, Thomas Prisner, Marina Bennati, Csaba Daday, Reinhard Kappl and Frauke Gräter ()
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Christopher Zapp: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35
Agnieszka Obarska-Kosinska: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35
Benedikt Rennekamp: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35
Markus Kurth: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35
David M. Hudson: University of Washington
Davide Mercadante: University of Zuerich, Winterthurerstr. 190
Uladzimir Barayeu: Heidelberg University, Im Neuenheimer Feld 234
Tobias P. Dick: DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280
Vasyl Denysenkov: Goethe University Frankfurt, Max-von-Laue-Str. 7
Thomas Prisner: Goethe University Frankfurt, Max-von-Laue-Str. 7
Marina Bennati: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11
Csaba Daday: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35
Reinhard Kappl: Saarland University Medical Center, CIPMM Geb. 48
Frauke Gräter: Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: Abstract As established nearly a century ago, mechanoradicals originate from homolytic bond scission in polymers. The existence, nature and biological relevance of mechanoradicals in proteins, instead, are unknown. We here show that mechanical stress on collagen produces radicals and subsequently reactive oxygen species, essential biological signaling molecules. Electron-paramagnetic resonance (EPR) spectroscopy of stretched rat tail tendon, atomistic molecular dynamics simulations and quantum-chemical calculations show that the radicals form by bond scission in the direct vicinity of crosslinks in collagen. Radicals migrate to adjacent clusters of aromatic residues and stabilize on oxidized tyrosyl radicals, giving rise to a distinct EPR spectrum consistent with a stable dihydroxyphenylalanine (DOPA) radical. The protein mechanoradicals, as a yet undiscovered source of oxidative stress, finally convert into hydrogen peroxide. Our study suggests collagen I to have evolved as a radical sponge against mechano-oxidative damage and proposes a mechanism for exercise-induced oxidative stress and redox-mediated pathophysiological processes.

Date: 2020
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DOI: 10.1038/s41467-020-15567-4

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