H2020Individual fellowship2021–2023

DYNAMIN · Deciphering collagen mineralization process by dynamic imaging in liquid

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2021-04-01 → 2023-03-31
EU contribution
€187,572
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

Deciphering collagen mineralization process by dynamic imaging in liquid

This MSC Action entitled ‘Deciphering collagen mineralization process by dynamic imaging in liquid’, aimed to gather dynamic information about the process of bone mineralization at the nanometer scale. The mechanisms governing bone formation, degradation and regeneration are still poorly understood, despite its clinical relevance. The social impact of a good bone health is remarkable, being a fundamental factor in ensuring a healthy aging population. The yearly economic burden of osteoporotic fractures in the EU is estimated at € 37 billion and expected to increase to € 47.4 billion in 2030. This fact indicates an imperative need to understand the mechanisms that determine bone mineralization and degradation, and to translate this knowledge to the clinics. The project was divided in two main parts: to unravel the dynamics of the mineral deposition pattern through the extracellular matrix; and to prove the role of one of the main proteoglycans (biglycan) as a promoter of mineralization.

Data: CORDIS, © European Union

Project objective

Bone is a complex nanocomposite with outstanding mechanical properties arising from the nanoscale interaction between its two main building blocks: type I collagen fibrils and hydroxyapatite crystals. Despite its clinical relevance, the mechanisms governing bone formation are still poorly understood, mainly due to the complexity of the processes. During bone formation and remodeling, non-collagenous proteins and proteoglycans act synergistically to regulate the mineral deposition process, participating in multiple signaling pathways involving regulatory molecules, osteoblasts and osteoclasts.Many of the studies performed until now relayed into simplified in vitro models that hardly represent this complexity. Furthermore, methods traditionally applied only provide snapshots of this process, unable to extract dynamic information. To really understand the mechanisms regulating bone mineralization, we need to simultaneously visualize its different components in its context, to be able to monitor their interactions. In this project, I propose to combining liquid-phase electron microscopy and immunolabelling, with which I aim to bring together dynamic imaging of a complex biochemical process and the identification of the biomacromolecules involved. By recreating the mineralization conditions inside the liquid cell, I aim to obtain real time data on nucleation sites, crystal growth and mineralization dynamics. The combination of dynamic imaging with immunogold will allow me to monitor the direct interaction of these regulatory molecules with the mineral particles at nanoscale resolution. By means of this new exciting approach I expect to provide unprecedented data on the processes of bone formation and take a step forward in the application of LPEM in biological materials.

Original text from CORDIS.

Participants

  • STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM · NijmegenCoordinatorNetherlands

Links

Data: CORDIS, © European Union