A multilevel, integrative approach for the study of cellmatrix mechanics and mechanotransduction during cell adhesion.

Cell-matrix mechanics is crucial for many physiological and pathophysiological processes. It affects cell adhesion, migration, proliferation and differentiation and is essential for understanding e.g. blood vessel formation, cancer metastasis and tissue regeneration and engineering. Cells probe the mechanical properties of the extracellular matrix (ECM) by applying tractional forces. The pericellular mechanical environment that in this way is being created depends on the ECM mechanical properties and on the cells active (contractile) and passive mechanical properties. Cell adhesion involves complex feedback mechanisms between mechanical and chemical signals that act at extracellular, cellular and subcellular length scales. In order to better understand these mechanisms, a multilevel integrative approach is needed that combines quantitative computational modelling and advanced microscopy methods, relating quantitative data at the different length scales. This project will establish such an approach. It will create an interdisciplinary platform for the study of cell adhesion in 3D fibrous ECMs (hydrogels), going across the boundaries of biomechanics, multiscale modelling and bio-imaging disciplines. It will result in clear methodological progress beyond the state of the art: a novel method for the calculation of tractional forces and a novel multilevel computational model of cell mechanics and mechanotransduction for a cell, embedded in a fibrous hydrogel will be established, by relying on data obtained by state of the art optical microscopy. This unique approach will generate new insight on the generic mechanisms that govern cell adhesion, which is highly relevant for many applications that involve cell culturing in a 3D environment, such as tissue engineering.

Keywords:Cell-matrix mechanics, Extracellular matrix, Multilevel integrative approach, Cell adhesion

Disciplines:Biomechanics