Dependence of cellular behaviour on viscosity defined ligand mobility in supported lipid bilayers

Q Science (General);QH301 Biology;QH345 Biochemistry

Bennett, Mark ; Engineering and Physical Sciences Research Council (EPSRC) ; Salmerón-Sánchez, Manuel

University:University of Glasgow

Department:School of Engineering

关键词: Molecular biology, supported lipid bilayers, cell biology, ligand mobilty, viscosity, biomaterials, cell response.;   

Others  :  http://theses.gla.ac.uk/30587/1/2018BennettPhD.pdf

来源: University of Glasgow

【 摘 要 】

This thesis has explored the nature of cellular behaviour in response to the mobility of ligands presented on supported lipid bilayers of varying viscosity (diffusive characteristics). This was inspired by the various characteristics of the in vivo microenvironment, controlling the cell response. For example, the viscoelastic, topographical, or chemical nature of the extracellular matrix can control cellular behaviours, such as adhesion, proliferation, migration and differentiation. Numerous biomaterials have alternately sought to understand the nature of the cell response and also to take advantage of it; the current work predominantly falls into the former of these categories. Whereas elastic stiffness is one side of the coin of viscoelasticity, viscosity is the other. Further, while much work has sought to understand the nature of both the elastic and viscoelastic nature of the cell response, as of yet few have sought to understand the role of viscosity in isolation. This is despite some work seeking to take advantage of this viscosity, by observing cellular behaviour on surfaces with known viscous components. This work has noted that cellular adhesion and spreading, focal adhesions, and differentiation are all affected by the viscous component of the surface without addressing why. Supported lipid bilayers (SLBs) present an excellent opportunity to understand these mechanisms. Commonly used as biosensing platforms, non-fouling coatings and model systems, they have also found use in both cell culture systems and in understanding mechanobiology. Individual lipids may exhibit a phase transition, Tm, at a temperature defined by the chemistry of the SLB component lipids; as such, they can exhibit significantly different, viscosity-defining, diffusive characteristics. This work describes the use of SLBs of differing Tm¬ that exhibit fluid-like or gel-like properties in cell culture conditions. These non-fouling SLBs were functionalised with the cell adhesive ligand RGD, derived from the matrix protein fibronectin, with the response of the cell on both the cell-wide and molecular scale determined. The cell response was then understood via pathways related to the mechanical sensing of the environment. Further, initial forays into the nature of the response of human mesenchymal stem cells (hMSCs) was determined, to test the applicability of the system to the overall field of biomedical engineering.