Dresden 2020 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 17: Poster V
BP 17.7: Poster
Dienstag, 17. März 2020, 14:00–16:00, P2/1OG
Mechanoradicals in tensed tendon collagen as a new source of oxidative stress — •Christopher Zapp1,2, Agnieszka Obarska-Kosinska1,3, Reinhard Kappl4, and Frauke Gräter1,5 — 1Heidelberg Institute for Theoretical Studies, Heidelberg — 2Institute for Theoretical Physics, Heidelberg University — 3Unit c/o DESY, European Molecular Biology Laboratory, Hamburg — 4Institute for Biophysics, Saarland University Medical Center, Homburg — 5Interdisciplinary Center for Scientific Computing, Heidelberg University
Mechanoradicals originate from homolytic bond scission in polymers. The existence, nature and biological relevance of mechanoradicals in proteins, instead, are unknown. We show that mechanical stress on collagen, a biopolymer, 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 calculations show that radicals form by covalent bond scission in collagen due to mechanical stress. Radicals migrate to adjacent clusters of oxidized aromatic residues radicals, giving rise to a distinct and stable 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 new mechanism for exercise-induced oxidative stress and redox-mediated pathophysiological processes.