Multiscale mathematical biology of cell-extracellular matrix interactions during morphogenesis

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Multiscale mathematical biology of cell-extracellular matrix interactions during morphogenesis

Type: Doctoral Thesis
Title: Multiscale mathematical biology of cell-extracellular matrix interactions during morphogenesis
Author: Rens, E.G.
Issue Date: 2018-06-27
Keywords: Mathematical biology
Cell-based modeling
Extracellular matrix
Biophysics
Mechanobiology
Abstract: 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
Promotor: Supervisor: Roeland M.H. Merks,
Faculty: Science
University: Leiden
Uri: urn:isbn:9789462999916
Handle: http://hdl.handle.net/1887/62863
 

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application/pdf Full text 26.82Mb Under embargo until 2019-06-27
application/pdf Title page_Contents 120.2Kb View/Open
application/pdf Chapter 1 Introduction 5.083Mb View/Open
application/pdf Chapter 2 3.536Mb View/Open Full text at publisher site
application/pdf Chapter 3 8.980Mb View/Open Full text at publisher site
application/pdf Chapter 4 2.782Mb Under embargo until 2019-06-27
application/pdf Chapter 5 3.014Mb View/Open Full text at publisher site
application/pdf Chapter 6 2.137Mb Under embargo until 2019-06-27
application/pdf Chapter 7 Discussion 2.016Mb View/Open
application/pdf Appendix 4.153Mb View/Open
application/pdf Bibliography 184.1Kb View/Open
application/pdf Summary 116.5Kb View/Open
application/pdf Summary in Dutch 100.9Kb View/Open
application/pdf Acknowledgements_Publications_Curriculum Vitae 125.0Kb View/Open
application/pdf Propositions 77.12Kb View/Open

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