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Title: A destruction/contraction gradient coordinates a persistent and polarized global actin flow to control cell directionality
Author: Yolland, Lawrence
ISNI:       0000 0004 7660 891X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Cell motility is hypothesised to be regulated by a step-wise series of events, beginning with leading-edge extension of the membrane. However, it is unclear how rapid leading-edge movements are capable of generating coordinated cell motion. Posterior to the leading edge is the flowing Actin network, which generates cellular propulsive forces. This flow is driven by a combination of Actin polymerisation pushing against the leading-edge, and myosin mediated contraction of the Actin network. Yet, it is unknown how this flow is organised and whether it is involved in controlling cell migration. Through the development of novel computational tools, I show that Actin retrograde flow in developmentally dispersing Drosophila macrophages is highly coherent. Mathematical analysis of Actin flow within macrophages reveals distinct regions of network compression, which are highly persistent in time compared with the leading edge. This data also highlights super-convergent regions within the flow field that represent a sudden transition from retrograde to anterograde Actin motion, whose polarity with respect to the nucleus strongly correlates with cell motion. This unveils a structure and asymmetry to global Actin flow within migrating cells, which I hypothesise is responsible for driving movement through a 'rear wheel drive' mechanism of cell migration as opposed to the putative leading-edge mediated 'front wheel drive' mechanism of directing cell motion.
Supervisor: Miodownik, M. ; Stramer, B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available