Project description
Regulation of extracellular matrix properties
The extracellular matrix (ECM) is a complex meshwork of proteins and carbohydrates within and surrounding tissues and organs, that enables cell adhesion and migration. ECM has a key role in development, cancer and wound healing, responding dynamically to different mechanical loads. The EU-funded VISCOMATRIX project aims to unveil the biophysical and molecular mechanisms that regulate ECM viscoelasticity and understand how it affects cell and tissue response. For this purpose, scientists will employ 3D materials and change various parameters to identify the key determinants of ECM viscoelasticity. Results will impact various biological fields, including tissue engineering and biomaterials design.
Objective
The mechanical properties of the extracellular matrix (ECM) regulate processes during development, cancer and wound healing. The vast majority of research efforts in this field have been focused on ECM’s elasticity as a leading determinant of cell and tissue behaviour. However, the ECM is not merely elastic but is instead both viscous and elastic. Due to its viscoelastic nature, the ECM response to mechanical loads is inherently dynamic and evolves with time, independently of matrix degradation or remodelling. Despite the universality of ECM’s viscoelasticity, how viscoelasticity affects tissue function is unknown. Based on our preliminary data, cellular behaviour diverges significantly between viscoelastic and elastic ECMs. We hypothesize that viscoelasticity dominates tissue response. Our objective is to determine the biophysical and molecular mechanisms that regulate viscoelasticity sensing and mechanotransduction in 3D and understand its implications in cell and tissue response. To address, we will use an integrative approach that will combine 3D materials with exquisite control of viscoelastic properties, systematic molecular perturbations, computational modelling and precise quantitative analysis of cellular properties, forces and stresses. While using these tools, we will unravel the molecular mechanisms that regulate viscoelasticity response at single-cell and collective level. We will determine the dynamic role of viscoelasticity in breast homeostasis, malignant transformation and invasion. Finally, we will validate the implications of viscoelasticity by measuring breast ECM’s viscoelastic properties and with in vivo experiments. We expect that this project will unravel novel mechanosensing mechanisms operating at the roots of biological responses. These mechanisms, due to the inherent viscoelastic nature of tissues, will affect many biological fields from morphogenesis to cancer, and applied fields such as tissue engineering and biomaterials design.
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Funding Scheme
ERC-STG - Starting GrantHost institution
WC2R 2LS London
United Kingdom