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(BBSRC DTP) States of prestress in intermediate filaments: the glassy state of cells


Project Description

The shape, mechanics and motility of cells is determined by an array of intracellular semi-flexible filaments. The array consists of microtubules, actins and intermediate filaments, such as vimentin, whose architectures are sensitively modulated with cross-linkers and motor proteins. Previously, using single molecule fluorescence microscopy, image analysis and new machine learning techniques [1,2,3], we demonstrated that semi-flexible peptides in vitro experience unusual quenched states of disorder i.e. they exist as an unusual soft glassy state of matter. We observed that even when the peptides are under no externally applied stress, a large number of individual filaments are under pre-stresses and are highly curved as a result [1,2]. The pre-stresses in turn have a huge impact on the majority of the physical properties of gels made from the peptides, including their mechanics. It is known that many semi-flexible filaments inside live cells also exist in high states of curvature and thus must also experience prestresses. With the new techniques developed for in vitro peptides, we expect to be able to rigorously quantify the states of prestress in intermediate filaments for the first time, providing a new window into their cellular biology and associated diseased states e.g. cancerous cells often have significantly modified cytoskeletal mechanics.

https://personalpages.manchester.ac.uk/staff/t.a.waigh/
https://www.research.manchester.ac.uk/portal/viki.allan.html
https://www.research.manchester.ac.uk/portal/martin.p.lowe.html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

[1] ‘Single-molecule study of peptide gel dynamics reveals states of prestress’, H.Cox, et al, Langmuir, 2018, 34, 14678-14689.
[2] ‘Active modulation of states of prestress in self-assembled short peptide gels’, H.Cox, et al, Biomacromolecules, 2019, 20, 1719-1730.
[3] ‘Some critical questions in biological physics: a guided tour around the bugbears’, T.A.Waigh, IOP, 2017.

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