Models for spatial organization of microtubules and cell polarization

Panagiotis Foteinopoulos

Research output: Thesisinternal PhD, WU

Abstract

The main actors in this PhD thesis are microtubules, dynamic polymers built from protein subunits that play many important roles in cells of all higher organisms. We study a number of their functions using mathematical modelling and computer simulations. First, we consider the role of microtubules in establishing the ordered cortical array, a structure that plays a key role in the plant cell elongation. We show theoretically that the observed effect that new microtubules are nucleated from pre-existing microtubules strongly enhances the order of the array and makes it more robust against variations in the conditions. Next, we turn to the role the shape of the cell plays in the spatial organization of microtubules. We show that depending on how the microtubules interact with the cell boundary, either the long or the short axis of the cell determines the majority direction of the microtubules.  Additionally, we formulate a model that predicts the positioning of the mitotic spindle, which is the cellular structure that segregates the duplicated chromosomes during eukaryotic cell division. We analyze how the speed, precision and final direction of the spindle orientation process depends on cell shape and the parameters that describe the microtubules. Finally, we turn to the potential role of microtubules in establishing cell polarity, the non-uniform distribution of cellular constituents, which is crucial for many developmental processes. Based solely on the propensity of microtubules to bind and transport proteins to the cell membrane, we set up a feasible and robust cell polarization mechanism, which could potentially be used to set up polarity in a minimal cell-like environment using a biochemical reconstitution approach. We study this model in its pure form in a perfectly spherical cell, in order to establish proof-of-principle, but also show that the effect remains in a more realistic non-spherical cell.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Mulder, Bela, Promotor
Award date12 Sep 2019
Place of PublicationWageningen
Publisher
Print ISBNs9789463950046
DOIs
Publication statusPublished - 2019

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polarization
cells
spindles
polarity
proteins
cell division
theses
chromosomes
organisms
positioning
elongation
computerized simulation
polymers
simulation

Cite this

Foteinopoulos, Panagiotis. / Models for spatial organization of microtubules and cell polarization. Wageningen : Wageningen University, 2019. 203 p.
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title = "Models for spatial organization of microtubules and cell polarization",
abstract = "The main actors in this PhD thesis are microtubules, dynamic polymers built from protein subunits that play many important roles in cells of all higher organisms. We study a number of their functions using mathematical modelling and computer simulations. First, we consider the role of microtubules in establishing the ordered cortical array, a structure that plays a key role in the plant cell elongation. We show theoretically that the observed effect that new microtubules are nucleated from pre-existing microtubules strongly enhances the order of the array and makes it more robust against variations in the conditions. Next, we turn to the role the shape of the cell plays in the spatial organization of microtubules. We show that depending on how the microtubules interact with the cell boundary, either the long or the short axis of the cell determines the majority direction of the microtubules.  Additionally, we formulate a model that predicts the positioning of the mitotic spindle, which is the cellular structure that segregates the duplicated chromosomes during eukaryotic cell division. We analyze how the speed, precision and final direction of the spindle orientation process depends on cell shape and the parameters that describe the microtubules. Finally, we turn to the potential role of microtubules in establishing cell polarity, the non-uniform distribution of cellular constituents, which is crucial for many developmental processes. Based solely on the propensity of microtubules to bind and transport proteins to the cell membrane, we set up a feasible and robust cell polarization mechanism, which could potentially be used to set up polarity in a minimal cell-like environment using a biochemical reconstitution approach. We study this model in its pure form in a perfectly spherical cell, in order to establish proof-of-principle, but also show that the effect remains in a more realistic non-spherical cell.",
author = "Panagiotis Foteinopoulos",
note = "WU thesis 7301 Includes bibliographical references. - With summaries in Dutch and English",
year = "2019",
doi = "10.18174/478734",
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Foteinopoulos, P 2019, 'Models for spatial organization of microtubules and cell polarization', Doctor of Philosophy, Wageningen University, Wageningen. https://doi.org/10.18174/478734

Models for spatial organization of microtubules and cell polarization. / Foteinopoulos, Panagiotis.

Wageningen : Wageningen University, 2019. 203 p.

Research output: Thesisinternal PhD, WU

TY - THES

T1 - Models for spatial organization of microtubules and cell polarization

AU - Foteinopoulos, Panagiotis

N1 - WU thesis 7301 Includes bibliographical references. - With summaries in Dutch and English

PY - 2019

Y1 - 2019

N2 - The main actors in this PhD thesis are microtubules, dynamic polymers built from protein subunits that play many important roles in cells of all higher organisms. We study a number of their functions using mathematical modelling and computer simulations. First, we consider the role of microtubules in establishing the ordered cortical array, a structure that plays a key role in the plant cell elongation. We show theoretically that the observed effect that new microtubules are nucleated from pre-existing microtubules strongly enhances the order of the array and makes it more robust against variations in the conditions. Next, we turn to the role the shape of the cell plays in the spatial organization of microtubules. We show that depending on how the microtubules interact with the cell boundary, either the long or the short axis of the cell determines the majority direction of the microtubules.  Additionally, we formulate a model that predicts the positioning of the mitotic spindle, which is the cellular structure that segregates the duplicated chromosomes during eukaryotic cell division. We analyze how the speed, precision and final direction of the spindle orientation process depends on cell shape and the parameters that describe the microtubules. Finally, we turn to the potential role of microtubules in establishing cell polarity, the non-uniform distribution of cellular constituents, which is crucial for many developmental processes. Based solely on the propensity of microtubules to bind and transport proteins to the cell membrane, we set up a feasible and robust cell polarization mechanism, which could potentially be used to set up polarity in a minimal cell-like environment using a biochemical reconstitution approach. We study this model in its pure form in a perfectly spherical cell, in order to establish proof-of-principle, but also show that the effect remains in a more realistic non-spherical cell.

AB - The main actors in this PhD thesis are microtubules, dynamic polymers built from protein subunits that play many important roles in cells of all higher organisms. We study a number of their functions using mathematical modelling and computer simulations. First, we consider the role of microtubules in establishing the ordered cortical array, a structure that plays a key role in the plant cell elongation. We show theoretically that the observed effect that new microtubules are nucleated from pre-existing microtubules strongly enhances the order of the array and makes it more robust against variations in the conditions. Next, we turn to the role the shape of the cell plays in the spatial organization of microtubules. We show that depending on how the microtubules interact with the cell boundary, either the long or the short axis of the cell determines the majority direction of the microtubules.  Additionally, we formulate a model that predicts the positioning of the mitotic spindle, which is the cellular structure that segregates the duplicated chromosomes during eukaryotic cell division. We analyze how the speed, precision and final direction of the spindle orientation process depends on cell shape and the parameters that describe the microtubules. Finally, we turn to the potential role of microtubules in establishing cell polarity, the non-uniform distribution of cellular constituents, which is crucial for many developmental processes. Based solely on the propensity of microtubules to bind and transport proteins to the cell membrane, we set up a feasible and robust cell polarization mechanism, which could potentially be used to set up polarity in a minimal cell-like environment using a biochemical reconstitution approach. We study this model in its pure form in a perfectly spherical cell, in order to establish proof-of-principle, but also show that the effect remains in a more realistic non-spherical cell.

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Foteinopoulos P. Models for spatial organization of microtubules and cell polarization. Wageningen: Wageningen University, 2019. 203 p. https://doi.org/10.18174/478734