Defined dissipative properties to investigate the role of matrix viscosity on cellular response

点击翻译按钮获取中文摘要

The overall aim of this proposal is to produce materials with defined dissipative propertiesto investigate the role of matrix viscosity on cellular response. Native tissues comprisecells and a dynamic extracellular matrix, which provides mechanical and biochemicalcues responsible for guiding cell adhesion, proliferation and differentiation. The majorityof synthetic materials utilised in mechanotransduction research are produced solely withdefined elastic properties, providing a static environment for which cells can grow.However, these materials fail to fully recapitulate the dissipative environment that cellsencounter in vivo (Cantini et al., 2019). Up to this point, little progress has been made inunderstanding how cells respond to matrix viscosity and how this can be engineered toinfluence cell fate. In this project, we propose to fabricate lipid-based and polymer-basedenvironments with defined range of viscous properties and controlled surface mobility.These material platforms will be utilised to elucidate the underlying cellular mechanismsbehind cell response to matrix viscosity. Furthermore, functionalisation of thesematerials with peptide ligands will be utilised to investigate interplay between celladhesion and matrix viscosity on cell behaviour. These platforms will improve ourunderstanding of how cells adhere and interact with viscous materials and how thisinfluences cell behaviour. Knowledge gained from these systems will then beincorporated into the fabrication of bulk hydrogel systems, which will be engineeredwith varying viscous properties, constant elastic properties and functionalised withvarying densities of peptide ligands. These hydrogel systems will be utilised to investigatethe interplay between matrix viscosity and elasticity on cell behaviour in two- and threedimensional environments. The outcomes of this project will improve our understandingof cellular response to matrix viscosity, paving the way for engineering of advancedmaterials with defined elastic and viscous properties for use in tissue engineering anddevelopment of in vitro tissue models with physiologically relevant mechanicalproperties.ReferencesCantini, M. et al. (2019) 'The Plot Thickens: The Emerging Role of Matrix Viscosity in CellMechanotransduction', Advanced Healthcare Materials. doi: 10.1002/adhm.201901259.