Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

The cartography of cell motion

Tools
- Tools
+ Tools

Tyson, R. A. (Richard Anthony) (2011) The cartography of cell motion. PhD thesis, University of Warwick.

[img]
Preview
Text
WRAP_THESIS_Tyson_2011.pdf - Submitted Version

Download (29Mb) | Preview
Official URL: http://webcat.warwick.ac.uk/record=b2581468~S1

Request Changes to record.

Abstract

Cell motility plays an important role throughout biology, the polymerisation of actin being fundamental in producing protrusive force. However, it is increasingly apparent that intracellular pressure, arising from myosin-II contraction, is a co-driver of motility. In its extreme form, pressure manifests itself as hemispherical protrusions, referred to as blebs, where membrane is torn from the underlying cortex. Although many components and signalling pathways have been identified, we lack a complete model of motility, particularly of the regulation and mechanics of blebbing. Advances in microscopy are continually improving the quality of time series image data, but the absence of highthroughput tools for extracting quantitative numbers remains an analysis bottle-neck. We develop the next generation of the successful QuimP software designed for automated analysis of motile cells, producing quantitative spatio-temporal maps of protein distributions and changes in cell morphology. Key to QuimP's new functionality, we present the Electrostatic Contour Migration Method (ECMM) that provides high resolution tracking of local deformation with better uniformity and efficiency than rival methods. Photobleaching experiments are used to give insight into the accuracy and limitations of in silico membrane tracking algorithms. We employ ECMM to build an automated protrusion tracking method (ECMM-APT) sensitive not only to pseudopodia, but also the complex characteristics of high speed blebs. QuimP is applied to characterising the protrusive behaviour of Dictyostelium, induced to bleb by imaging under agar. We show blebs are characterised by distinct speed-displacement distributions, can reach speeds of 4.9μm/sec, and preferentially form at the anks during chemotaxis. Significantly, blebs emerge from at

to concave membrane regions suggesting curvature is a major determinant of bleb location, size, and speed. We hypothesise that actin driven pseudopodia at the leading edge induce changes in curvature and therefore membrane tension, positive curvature inhibiting blebbing at the very front, and negative curvature enhancing blebbing at the sides. This possibly provides the necessary space for rear advancement. Furthermore, bleb kymographs reveal a retrograde shift of the cortex at the point of bleb expansion, suggesting inward contractive forces acting on the cortex even at concave regions. Strains defficient in phospholipid signalling show impaired chemotaxis and blebbing. Finally, we present further applications of QuimP, for example, we conclusively show that dishevelled is not polarised during Xenopus gastrulation, contrary to hypotheses in the literature.

Item Type: Thesis (PhD)
Subjects: Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Headings (LCSH): Cells -- Motility -- Computer programs
Official Date: December 2011
Dates:
DateEvent
December 2011Submitted
Institution: University of Warwick
Theses Department: Systems Biology Doctoral Training Centre
Thesis Type: PhD
Publication Status: Unpublished
Supervisor(s)/Advisor: Bretschneider, Till
Extent: xvii, 174 leaves : ill., charts
Language: eng

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us