Universiteit Leiden

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Proefschrift

Multiscale mathematical biology of cell-extracellular matrix interactions during morphogenesis

During embryonic growth, cells proliferate, differentiate, and collectively migrate to form different tissues at the right position and time in the body.

Auteur
Rens, E.G.
Datum
27 juni 2018
Links
Thesis in Leiden Repository

During embryonic growth, cells proliferate, differentiate, and collectively migrate to form different tissues at the right position and time in the body. The extracellular matrix, a gel-like material containing an intricate network of fibres that surrounds cells in tissues affects cell shape and cell migration. Cells can sense the mechanical properties of the matrix, such as its stiffness, by applying forces on the matrix. In response to matrix stiffness, cells change their shape and migratory behaviour. Cells communicate with neighbouring cells by applying forces on the matrix that locally stiffen the matrix. In this thesis, we study how such mechanical cell-cell communication coordinates the patterning of tissues. We have developed multiscale models that describe cell shape and migration, the extracellular matrix and cell-matrix interactions. Our simulations suggest that by communicating via forces on the matrix, cells can form networks. This process resembles dynamics of a cell culture model of blood vessel formation. Furthermore, simulated tissues that actively pull on the matrix can better align to pre-existing stresses in the matrix compared to less contractile tissues. A model that includes the molecular complexes mediating cell-matrix interactions can accurately predict how cell shape and cell motility depends on matrix stiffness.

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