Cell sensing of micro- and nano-topography

Hartley, Robert (2002) Cell sensing of micro- and nano-topography. PhD thesis, University of Glasgow.

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In this thesis I have assessed the reaction of endothelia and epithelia to micro and nano-topography. I specifically analysed the movement, cytoskeletal reaction and signal transduction mechanisms involved. I have shown that irrespective of subjective morphology, the substratum topography underlying cells had the ability to affect the cytoskeletal alignment and directionality of induced movement. The reaction of the three main elements of the cytoskeleton; actin fibres, intermediate filaments and microtubules, had different basal-apical distributions and were oriented along the grooves. Particularly significant was my description of growth factor induced, directed movement of MDCK epithelia on grooved topography. This directed movement was observed whether the cells were elongated individual cells or non-morphologically reactive multicellular monolayers. Movement was shown to flow along the grooves. This directionality may have particular relevance in the repair of lesions or situations where one requires differential positioning or migration of cell types (Babu and Wells 2001). I also assessed the possibility of unidirectional guidance using a surface with major grooves for bi-directional elongation. This particular surface* had gradients in the troughs to confer unidirectional movement. I also show that a grooved topographical substrate, analogous to fibre dimensions encountered in-vivo, rescues inhibition of cell-spreading (by signal pathway blockade) in the direction of the groove but not anti-parallel. The spreading was dependent on groove depth and is consistent with elongation on variable depths. 1 propose a new hypothesis that bi-directional signalling mechanisms are involved in cell spreading, and elongation is by a different mechanism from lateral spreading. Recently, following this work and during the final writing of this thesis, a bidirectional spreading hypothesis has also been speculated by Levina et al (2001). In this paper only the phenotypic observation noticed by Curtis and Clark, Brunette, and Dunn was described, but with emphasis on cell width rather than elongation. I have further qualified the hypothesis by showing the lateral spreading reaction, but not elongation, is controlled by two signalling pathways, PI3-kinase and MAPK. When blocked, these inhibit the radial spreading reaction on flat surfaces.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Adam Curtis
Keywords: Cellular biology
Date of Award: 2002
Depositing User: Enlighten Team
Unique ID: glathesis:2002-71966
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 13:36
Last Modified: 17 May 2019 13:36
URI: https://theses.gla.ac.uk/id/eprint/71966

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