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RADICOL

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Mechanoradicals in Collagen

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 c... ver más

31/05/2026

UHEI

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

RUPRECHTKARLSUNIVERSITAET HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-01-27

ERC-2020-COG: ERC CONSOLIDATOR GRANTS

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2 Participantes

UHEI

2.00M€ | Lider

SILOS CORDOBA

582.97K€ | Participante

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Duración del proyecto: 64 meses Fecha Inicio: 2021-01-27
Fecha Fin: 2026-05-31

Líder del proyecto

RUPRECHTKARLSUNIVERSITAET HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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