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Mechanoradicals in Collagen

Project description

The role of mechanoradicals in collagen mechanosensation and ageing

It has been long known that synthetic polymers subjected to mechanical stress generate mechanoradicals by rupture of chemical bonds. The nature and biological relevance of mechanoradicals in proteins remain unknown. Yet collagen is the main structural protein of numerous organic connective tissues, the ageing of which is a fundamental problem in healthcare. The EU-funded RADICOL project proposes to investigate the role of mechanoradicals in the ageing of biomaterials in a computational and experimental approach. Quantum chemical calculations and molecular dynamics simulations will allow the identification of bonds and subsequent radical reactions in atomistic collagen. These computational predictions will then be tested by biochemical and biophysical experiments. The project will shed new light on biological mechanosensation and ageing.


Our tissues, in particular collagen as the most abundant protein in our body, are constantly exposed to mechanical loads, reaching multiples of the body weight. In artificial polymers, mechanical loads are known for a century to cause radical formation and chemical degradation processes. Mechanoradicals from bond ruptures, being highly reactive and oxidising, deteriorate the material, leading to stiffening and ageing. Ageing of organic tissue is a fundamental problem in health and disease, but a role of mechanoradicals has been a blind spot. Our simple but novel idea is to test the role of mechanoradicals for ageing of biomaterials. As a starting point, we have recently uncovered mechanoradicals in tensed tendon collagen. They readily react with water to form reactive oxygen species (ROS), key signalling molecules in a multitude of physiological processes including ageing.
I hypothesise that mechanoradicals generate a feedback loop resulting in accelerated collagen ageing. Using a scale-bridging combined computational and experimental approach, I will dissect the full lifecycle of mechanoradicals in collagen, from bond scission and radical migration to ROS formation, to uncover new mechanisms of radical-mediated ageing. We will perform quantum chemical calculations and Molecular Dynamics (MD) simulations, including a new reactive Monte Carlo/MD scheme, to identify scissile bonds and subsequent radical reactions in atomistic collagen I fibril models. For validation, a combination of electron-paramagnetic resonance spectroscopy, mass spectrometry and other biophysical experiments will be employed to measure degradation pathways, radicals and ROS under varying crosslink densities and types as present in young, aged and diseased tendon tissues.
RADICOL will establish protein mechanoradicals as an as yet uncovered source of oxidative stress, and as a new paradigm of biological mechanosensation and ageing.


Net EU contribution
€ 1 998 873,00
Seminarstrasse 2
69117 Heidelberg

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Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00

Beneficiaries (1)