Periodic Reporting for period 5 - COLMIN (A Google Earth Approach to Understanding Collagen Mineralization)
Periodo di rendicontazione: 2024-02-01 al 2025-04-30
The COLMIN project set out to solve one of the most fundamental yet poorly understood processes in biology: how collagen — the body’s most abundant protein — becomes mineralized to form bone. This process is crucial for healthy bone development, and when it fails, it can lead to serious conditions such as osteoporosis, osteogenesis imperfecta, and other mineralization disorders.
Understanding how collagen mineralizes at the nanoscale, in both healthy and pathological conditions, is essential for developing new treatments, designing better biomaterials, and advancing regenerative medicine. Despite its importance, the process had remained largely a black box due to technological limitations.
COLMIN aimed to break that barrier by combining cutting-edge imaging technologies, in vitro models, and interdisciplinary research. The goal was to visualize — in real time and in 3D — how bone forms, how collagen and minerals interact, and what goes wrong in disease. Ultimately, COLMIN’s objective was to redefine the standard of how we study and understand bone biology at the molecular level.
Understanding how collagen mineralizes at the nanoscale, in both healthy and pathological conditions, is essential for developing new treatments, designing better biomaterials, and advancing regenerative medicine. Despite its importance, the process had remained largely a black box due to technological limitations.
COLMIN aimed to break that barrier by combining cutting-edge imaging technologies, in vitro models, and interdisciplinary research. The goal was to visualize — in real time and in 3D — how bone forms, how collagen and minerals interact, and what goes wrong in disease. Ultimately, COLMIN’s objective was to redefine the standard of how we study and understand bone biology at the molecular level.
Over the course of the project, COLMIN made significant strides across multiple complementary research lines:
Developing a 3D bone organoid model: The team created a fully living 3D model of early-stage bone formation using human stem cells. This "bone organoid" mimics key features of real bone tissue, including osteocytes embedded in a mineralized collagen matrix. It enables long-term, real-time studies of bone development under both normal and pathological conditions.
Engineering a bone-on-a-chip system: A microfluidic platform was developed to allow live imaging of bone tissue formation under mechanical stress. The chip allows scientists to precisely control and monitor tissue behavior, and the approach was published as a preprint with broad potential in disease modeling and drug screening.
Establishing next-generation imaging workflows: COLMIN developed a novel 3D cryo-correlative workflow that integrates light, electron, and Raman microscopy at cryogenic temperatures. This technique can map the structure and chemistry of tissues at nanometer resolution without damaging them. The workflow has since been commercialized through a collaboration with ZEISS.
Breakthroughs in collagen biology: The project uncovered a previously unrecognized membrane-less pathway for collagen secretion and showed how chemical modifications, such as overglycosylation, impact the organization and mineralization of collagen fibrils — findings relevant for diseases like brittle bone disease.
Insights into bone mineralization mechanisms: COLMIN demonstrated how different forms of calcium-phosphate particles contribute to bone formation, how mineral crystals align within and between collagen fibrils, and how sugars and metabolic acids influence mineral shape, growth, and orientation.
Dissemination and societal impact: COLMIN research contributed to a high-profile study on COVID-19 kidney infection, highlighted on national Dutch television with over 200,000 viewers. Findings were also shared widely through high-impact journals (e.g. Nature Communications, Advanced Functional Materials, Communications Biology), public preprints, conferences, and direct collaborations with industry and clinical partners.
Exploitation of results: The 3D cryo-correlative workflow is now a product used commercially. The expertise built in COLMIN led to the founding of a new national electron microscopy center (BIOMATEM), a €2M investment, and the award of a second ERC Advanced Grant (REVALVE) to continue the work in disease contexts.
Developing a 3D bone organoid model: The team created a fully living 3D model of early-stage bone formation using human stem cells. This "bone organoid" mimics key features of real bone tissue, including osteocytes embedded in a mineralized collagen matrix. It enables long-term, real-time studies of bone development under both normal and pathological conditions.
Engineering a bone-on-a-chip system: A microfluidic platform was developed to allow live imaging of bone tissue formation under mechanical stress. The chip allows scientists to precisely control and monitor tissue behavior, and the approach was published as a preprint with broad potential in disease modeling and drug screening.
Establishing next-generation imaging workflows: COLMIN developed a novel 3D cryo-correlative workflow that integrates light, electron, and Raman microscopy at cryogenic temperatures. This technique can map the structure and chemistry of tissues at nanometer resolution without damaging them. The workflow has since been commercialized through a collaboration with ZEISS.
Breakthroughs in collagen biology: The project uncovered a previously unrecognized membrane-less pathway for collagen secretion and showed how chemical modifications, such as overglycosylation, impact the organization and mineralization of collagen fibrils — findings relevant for diseases like brittle bone disease.
Insights into bone mineralization mechanisms: COLMIN demonstrated how different forms of calcium-phosphate particles contribute to bone formation, how mineral crystals align within and between collagen fibrils, and how sugars and metabolic acids influence mineral shape, growth, and orientation.
Dissemination and societal impact: COLMIN research contributed to a high-profile study on COVID-19 kidney infection, highlighted on national Dutch television with over 200,000 viewers. Findings were also shared widely through high-impact journals (e.g. Nature Communications, Advanced Functional Materials, Communications Biology), public preprints, conferences, and direct collaborations with industry and clinical partners.
Exploitation of results: The 3D cryo-correlative workflow is now a product used commercially. The expertise built in COLMIN led to the founding of a new national electron microscopy center (BIOMATEM), a €2M investment, and the award of a second ERC Advanced Grant (REVALVE) to continue the work in disease contexts.
COLMIN pushed the frontiers of imaging, modeling, and understanding of bone biology:
It delivered the most advanced in vitro bone model to date, capable of mimicking real tissue development.
It established the first reliable nanoscale live imaging of mineral formation in a biological context.
It developed and validated a workflow that correlates structure, chemistry, and function at sub-cellular resolution, now adopted by industry.
It provided mechanistic insights into collagen-mineral interactions, helping to rewrite the textbook understanding of bone formation.
The project’s impact extends far beyond its original scope. It changed how researchers study tissue mineralization, gave rise to new technologies and collaborations, and positioned its team and host institution as global leaders in bone research and electron microscopy. These breakthroughs now feed directly into the follow-up ERC project, REVALVE, where the team will investigate how these processes change in diseased states.
It delivered the most advanced in vitro bone model to date, capable of mimicking real tissue development.
It established the first reliable nanoscale live imaging of mineral formation in a biological context.
It developed and validated a workflow that correlates structure, chemistry, and function at sub-cellular resolution, now adopted by industry.
It provided mechanistic insights into collagen-mineral interactions, helping to rewrite the textbook understanding of bone formation.
The project’s impact extends far beyond its original scope. It changed how researchers study tissue mineralization, gave rise to new technologies and collaborations, and positioned its team and host institution as global leaders in bone research and electron microscopy. These breakthroughs now feed directly into the follow-up ERC project, REVALVE, where the team will investigate how these processes change in diseased states.