{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/386153"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/386153","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Experimental and Computational Modelling of Tissue Rheology and Mechanics in Morphogenesis","abstract":"In this thesis, we report two tissue models designed to investigate how key cellular mechanical parameters interact with tissue material properties and active cell behaviour to drive tissue deformation in the context of biological development. Firstly, an experimental, three-dimensional tissue model is presented, which consists of giant unilamellar vesicles decorated with cell-cell linker molecules. Cell-cell adhesion and cell membrane tension are controlled to influence tissue-scale mechanical properties. The first results chapter of this part introduces novel protocols on the production of a tissue mimic at a large enough scale to characterise tissue rheology. In the next chapter, the experimental microrheological setup, material characterisation tests and the numerical fitting methods used to determine rheological properties are detailed. Finally, prediction methods to map microstructural parameters to bulk rheology are outlined in the final chapter. The experimental model is found to exhibit a rich, power-law behaviour that is characterised using fractional rheology. Remarkably, the variation in emergent rheology is captured using a single scalar parameter. In addition, a kernel-based prediction method is shown to possess significant power in predicting bulk rheology as a function of experimentally controlled cell-scale parameters. This part demonstrates that the rich rheological tissue behaviour can be reproduced using a simple model with few experimentally controlled parameters. Secondly, we introduce a cell-scale computational model for epithelial tissues to investigate the role of cell material properties, mechanical forces and boundary conditions on tissue deformation rates. In the first chapter, we introduce the model with a particular focus on mechanical force balance and cell-cell dynamics, including elastic forces due to deformation, viscous dissipation due to plastic remodelling and active migratory and contractile forces. In the next chapter, the model is shown to recapitulate various complex active behaviours relevant to morphogenesis, including cell migration and convergence-extension. The mechanical interaction between the active tissue and its external environment was found to significantly alter the deformation profile. In the final results chapter, using standard rheological characterisation tests, the model is also shown to exhibit tissue viscoelastic characteristics, with cellular parameters directly mapping into rheological ones. How quickly active processes drive tissue deformation was found to be governed by cell and tissue rheological properties. Moreover, we show that tissue flow, either actively driven by internal forces or externally driven with passive ones, leaves a universal microstructural fingerprint. Thus, we demonstrate how the interaction between forces and tissue material properties can regulate cell morphology.","abstract_html":"In this thesis, we report two tissue models designed to investigate how key cellular mechanical parameters interact with tissue material properties and active cell behaviour to drive tissue deformation in the context of biological development. Firstly, an experimental, three-dimensional tissue model is presented, which consists of giant unilamellar vesicles decorated with cell-cell linker molecules. Cell-cell adhesion and cell membrane tension are controlled to influence tissue-scale mechanical properties. The first results chapter of this part introduces novel protocols on the production of a tissue mimic at a large enough scale to characterise tissue rheology. In the next chapter, the experimental microrheological setup, material characterisation tests and the numerical fitting methods used to determine rheological properties are detailed. Finally, prediction methods to map microstructural parameters to bulk rheology are outlined in the final chapter. The experimental model is found to exhibit a rich, power-law behaviour that is characterised using fractional rheology. Remarkably, the variation in emergent rheology is captured using a single scalar parameter. In addition, a kernel-based prediction method is shown to possess significant power in predicting bulk rheology as a function of experimentally controlled cell-scale parameters. This part demonstrates that the rich rheological tissue behaviour can be reproduced using a simple model with few experimentally controlled parameters. Secondly, we introduce a cell-scale computational model for epithelial tissues to investigate the role of cell material properties, mechanical forces and boundary conditions on tissue deformation rates. In the first chapter, we introduce the model with a particular focus on mechanical force balance and cell-cell dynamics, including elastic forces due to deformation, viscous dissipation due to plastic remodelling and active migratory and contractile forces. In the next chapter, the model is shown to recapitulate various complex active behaviours relevant to morphogenesis, including cell migration and convergence-extension. The mechanical interaction between the active tissue and its external environment was found to significantly alter the deformation profile. In the final results chapter, using standard rheological characterisation tests, the model is also shown to exhibit tissue viscoelastic characteristics, with cellular parameters directly mapping into rheological ones. How quickly active processes drive tissue deformation was found to be governed by cell and tissue rheological properties. Moreover, we show that tissue flow, either actively driven by internal forces or externally driven with passive ones, leaves a universal microstructural fingerprint. Thus, we demonstrate how the interaction between forces and tissue material properties can regulate cell morphology.","abstract_has_math":false,"creators":["Basar, Fikret"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Kabla, Alexandre"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-12-22","date_published":"2024-12-22","updated_at":"2026-07-22T22:24:08Z","subjects":["Morphogenesis","Tissue Rheology","Computational Biomechanics","Convergence-extension","Migration","Cell-cell dissipation","Biophysics"],"languages":[],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/50f4cf6d-07d0-4ffd-bb3d-4885574db2a7/download","http://purl.org/NET/rdflicense/allrightsreserved"],"identifier_entries":[{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000313774585"],"render_values":[{"text":"0000-0003-1377-4585","href":"https://orcid.org/0000-0003-1377-4585","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.119495","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kabla, Alexandre"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["EPSRC"]},{"key":"dc:creator","label":"Author","values":["Basar, Fikret"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000313774585"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2024-12-22"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/386153"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Morphogenesis","Tissue Rheology","Computational Biomechanics","Convergence-extension","Migration","Cell-cell dissipation","Biophysics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/50f4cf6d-07d0-4ffd-bb3d-4885574db2a7/download","http://purl.org/NET/rdflicense/allrightsreserved"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.17863/CAM.119495"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/0fc883bc-ac5a-41a0-bcdb-5d596cb055f5/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In this thesis, we report two tissue models designed to investigate how key cellular mechanical parameters interact with tissue material properties and active cell behaviour to drive tissue deformation in the context of biological development. 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In addition, a kernel-based prediction method is shown to possess significant power in predicting bulk rheology as a function of experimentally controlled cell-scale parameters. This part demonstrates that the rich rheological tissue behaviour can be reproduced using a simple model with few experimentally controlled parameters. Secondly, we introduce a cell-scale computational model for epithelial tissues to investigate the role of cell material properties, mechanical forces and boundary conditions on tissue deformation rates. In the first chapter, we introduce the model with a particular focus on mechanical force balance and cell-cell dynamics, including elastic forces due to deformation, viscous dissipation due to plastic remodelling and active migratory and contractile forces. In the next chapter, the model is shown to recapitulate various complex active behaviours relevant to morphogenesis, including cell migration and convergence-extension. The mechanical interaction between the active tissue and its external environment was found to significantly alter the deformation profile. In the final results chapter, using standard rheological characterisation tests, the model is also shown to exhibit tissue viscoelastic characteristics, with cellular parameters directly mapping into rheological ones. How quickly active processes drive tissue deformation was found to be governed by cell and tissue rheological properties. Moreover, we show that tissue flow, either actively driven by internal forces or externally driven with passive ones, leaves a universal microstructural fingerprint. 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In addition, a kernel-based prediction method is shown to possess significant power in predicting bulk rheology as a function of experimentally controlled cell-scale parameters. This part demonstrates that the rich rheological tissue behaviour can be reproduced using a simple model with few experimentally controlled parameters. Secondly, we introduce a cell-scale computational model for epithelial tissues to investigate the role of cell material properties, mechanical forces and boundary conditions on tissue deformation rates. In the first chapter, we introduce the model with a particular focus on mechanical force balance and cell-cell dynamics, including elastic forces due to deformation, viscous dissipation due to plastic remodelling and active migratory and contractile forces. In the next chapter, the model is shown to recapitulate various complex active behaviours relevant to morphogenesis, including cell migration and convergence-extension. 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