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Mechanosensation through radicals in tensed collagen

Thursday (22.03.2018)
13:20 - 13:40
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Biological tissues are subjected to vastly varying levels of mechanical load. Protein regulation by force-induced conformational changes has been established as a crucial mode of mechanosensing.

However, protein-based biological materials like skin, cartilage, and tendon can experience excessive stresses all the way up to tissue rupture. Whether and how covalent bond scission in stressed protein materials could contribute to mechanosensing remains unknown. We addressed this question for collagen, the most abundant protein in humans, the major force-bearing component of essentially all tissues, and a heavily crosslinked biopolymer.

Using combined rheology and electron paramagnetic resonance (EPR) experiments, we show that physiological levels of stress on collagen fibrils from rat tail tendon lead to the formation of mechano-radicals by covalent bond rupture. Radical formation increases with the level of applied stress and occurs already much before fiber rupture.

We identify specific bonds in the lysine-based crosslinks as points of stress concentration in tensed fibers through classical molecular dynamics simulations. Using high-level quantum calculations, we establish the chemical nature of the scission to be homolytic. The radicals subsequently undergo rapid reactions with water, yielding reactive oxygen species. Taken together, our study proposes a new mode of coupling between mechanical and oxidative stress in collagen-based tissues as a missing link between mechanical load and biological processes, from pain sensation to inflammation.

Christopher Zapp
HITS - Heidelberg Institute für Theoretical Studies
Additional Authors:
  • Dr. Agnieszka Obarska-Kosinska
    Heidelberg Institute for Theoretical Studies (HITS)
  • Dr. Csaba Daday
    Heidelberg Institute for Theoretical Studies (HITS)
  • Dr. Reinhard Kappl
    Saarland University Medical Center
  • Prof. Dr. Frauke Gräter
    Heidelberg Institute for Theoretical Studies (HITS)