Ng, Tin Wai (Jessica);
(2025)
Understanding states of suspended animation in living cells.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
In response to severe metabolic stresses, many organisms can enter a reversible state known as suspended animation (SA), in which all observable activities, such as growth and motility, come to a halt. Remarkably, after the restoration of metabolism, they can resume their activities, unharmed. Many intracellular activities depend on the orderly structures formed by the cytoskeleton, which consists of self-organising biopolymers dependent on energy derived from metabolism. Yet, how the cytoskeleton organisation is perturbed upon SA is little understood. Here I used dividing mammalian cells as a model to probe the effect of SA on the cytoskeleton. I observed that the mitotic spindle shrank significantly and reached a new steady state size upon treatment with metabolic inhibitors that mimics SA conditions. Meanwhile, chromosome alignment and spindle bipolarity appeared largely unaffected. After the restoration of metabolism, the spindle could recover its size and complete division. I investigated how energy amount, the density and the dynamics of microtubules (MTs) were altered during spindle shrinkage. MT depolymerisation and energy-dependent motor activities were lost before the stabilisation of spindle size. Meanwhile, the antiparallel MT overlap region decorated by PRC1 lengthened during spindle shrinkage. Using the experimental results, I modified the force balance model from a previous study. It predicted that the spindle underwent elastic recovery after MT depolymerisation was completed. Cytoplasm removal and simultaneous energy depletion accelerated spindle shrinkage, suggesting that the cytoplasm limited the rate of shrinkage and that the spindle was subjected to tensile strain prior to energy depletion. Overall, this showed that the spindle can adapt to energy shortage by reorganising into an intermediate structure without completely losing structural integrity. The intrinsic viscoelasticity of the passive spindle serves to stabilise its structure.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Understanding states of suspended animation in living cells |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10205853 |
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