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Title: Microscopy of interactions at the cell-material and cell-matrix interface
Author: Hansel, Catherine Sarah
ISNI:       0000 0004 8504 4669
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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This PhD project investigates how mechanical and biochemical cues from the microenvironment regulate fundamental aspects of cell behaviour, using both synthetically and naturally derived systems, and places a particular emphasis on the application of microscopy as a means to elucidate these interactions. Firstly, porous silicon nanoneedle (nN) arrays are used as a synthetic material to study cellular mechanotransduction; the mechanism by which cells transduce mechanical forces into biochemical signals. Nanoneedles are able to tightly interface with cells and can therefore act as a tool to directly probe and manipulate cells. The interaction between nN and two primary human cell types is assessed: human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs). In this work, nN are shown to interact with multiple organelles in primary human cells and these findings have implications for the design of nanomaterial biointerfaces to study and influence cell behaviour and to administer cargo. Secondly, a naturally-cleaved extracellular matrix (ECM) protein fragment (laminin-β1 fragment) is used to explore how cryptic ECM sites affect biochemical signalling pathways in cells. The epithelial-to-mesenchymal transition (EMT) is initiated by transforming growth factor beta (TGF-β) in normal murine mammary gland epithelial (NMuMG) cells in the presence and absence of a laminin β1-fragment, and the effects of the laminin β1-fragment on EMT are explored. This includes an assessment of the biochemical signalling pathways involved in EMT, and cell migration studies. By studying the molecular basis of EMT through a range of microscopy techniques, insight can be provided into a process that is pivotal in cancer metastasis and that is a feature of inflammatory and fibrotic responses.
Supervisor: Stevens, Molly ; Cass, Tony Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral