Stephanie Portet - Profile on Academia.edu (original) (raw)

Papers by Stephanie Portet

Research paper thumbnail of Dual-wavelength stopped-flow analysis of the lateral and longitudinal assembly kinetics of vimentin

Vimentin is a highly charged intermediate filament protein that inherently forms extended dimeric... more Vimentin is a highly charged intermediate filament protein that inherently forms extended dimeric coiled-coils, which serve as the basic building blocks of intermediate filaments. Under low ionic strength conditions, vimentin filaments dissociate into uniform tetrameric complexes of two anti-parallel oriented, half-staggered coiled-coil dimers. By addition of salt, vimentin tetramers spontaneously reassemble into filaments in a time-dependent process: i) lateral assembly of tetramers into unit-length filaments (ULFs); ii) longitudinal annealing of ULFs; iii) longitudinal assembly of filaments coupled with subsequent radial compaction. To independently determine the lateral and longitudinal assembly kinetics, we measure with a stopped-flow instrument the static light scattering signal at two different wavelengths (405 and 594 nm) with a temporal resolution of 3 ms, and analyze the signals based on Rayleigh-Gans theory. This theory considers that the intensity of the scattered light d...

Research paper thumbnail of Models of Vimentin Organization Under Actin-Driven Transport

arXiv (Cornell University), Sep 6, 2022

Intermediate filaments form an essential structural network, spread throughout the cytoplasm and ... more Intermediate filaments form an essential structural network, spread throughout the cytoplasm and play a key role in cell mechanics, intracellular organization and molecular signaling. The maintenance of the network and its adaptation to the cell's dynamic behavior relies on several mechanisms implicating cytoskeletal crosstalk which are not fully understood. Mathematical modeling allows us to compare several biologically realistic scenarios to help us interpret experimental data. In this study, we observe and model the dynamics of the vimentin intermediate filaments in single glial cells seeded on circular micropatterns following microtubule disruption by nocodazole treatment. In these conditions, the vimentin filaments move towards the cell center and accumulate before eventually reaching a steady-state. In absence of microtubule-driven transport, the motion of the vimentin network is primarily driven by actin-related mechanisms. To model these experimental findings, we hypothesize that vimentin may exist in two states, mobile and immobile, and switches between the states at unknown (either constant or non-constant) rates. Mobile vimentin are assumed to advect with either constant or non-constant velocity. We introduce several biologically realistic scenarios using this set of assumptions. For each scenario, we use differential evolution to find the best parameter sets resulting in a solution that most closely matches the experimental data, then the assumptions are evaluated using the Akaike Information Criterion. This modeling approach allows us to conclude that our experimental data are best explained by a spatially dependent trapping of intermediate filaments or a spatially dependent speed of actin-dependent transport.

Research paper thumbnail of Quarantine and the risk of COVID-19 importation

Epidemiology and Infection, Dec 9, 2020

Using a stochastic model, we assess the risk of importation-induced local transmission chains in ... more Using a stochastic model, we assess the risk of importation-induced local transmission chains in locations seeing few or no local transmissions and evaluate the role of quarantine in the mitigation of this risk. We find that the rate of importations plays a critical role in determining the risk that case importations lead to local transmission chains, more so than local transmission characteristics, i.e. strength of social distancing measures (NPI). The latter influences the severity of the outbreaks when they do take place. Quarantine after arrival in a location is an efficacious way to reduce the rate of importations. Locations that see no or low-level local transmission should ensure that the rate of importations remains low. A high level of compliance with post-arrival quarantine followed by testing achieves this objective with less of an impact than travel restrictions or bans.

Research paper thumbnail of Epidemiological implications of mobility between a large urban centre and smaller satellite cities

Journal of Mathematical Biology, Jan 14, 2015

An SIR infectious disease propagation model is considered that incorporates mobility of individua... more An SIR infectious disease propagation model is considered that incorporates mobility of individuals between a large urban centre and smaller satellite cities. Because of the difference in population sizes, the urban centre has standard incidence and satellite cities have mass action incidence. It is shown that the general basic reproduction number R 0 acts as a threshold between global asymptotic stability of the disease free equilibrium and disease persistence. The case of Winnipeg (MB, Canada) and some neighbouring satellite communities is then considered numerically to complement the mathematical analysis, highlighting the importance of taking into account not only R 0 but also other measures of disease severity. It is found that the large urban centre governs most of the behaviour of the general system and control of the spread is better achieved by targeting it rather than reducing movement between the units. Also, the capacity of a satellite city to affect the general system depends on its population size and its connectivity to the main urban centre.

Research paper thumbnail of Using Fluorescence Recovery After Photobleaching data to uncover filament dynamics

PLOS Computational Biology

Fluorescence Recovery After Photobleaching (FRAP) has been extensively used to understand molecul... more Fluorescence Recovery After Photobleaching (FRAP) has been extensively used to understand molecular dynamics in cells. This technique when applied to soluble, globular molecules driven by diffusion is easily interpreted and well understood. However, the classical methods of analysis cannot be applied to anisotropic structures subjected to directed transport, such as cytoskeletal filaments or elongated organelles transported along microtubule tracks. A new mathematical approach is needed to analyze FRAP data in this context and determine what information can be obtain from such experiments. To address these questions, we analyze fluorescence intensity profile curves after photobleaching of fluorescently labelled intermediate filaments anterogradely transported along microtubules. We apply the analysis to intermediate filament data to determine information about the filament motion. Our analysis consists of deriving equations for fluorescence intensity profiles and developing a mathem...

Research paper thumbnail of Spread of Dutch elm disease in an urban forest

Ecological Modelling, 2020

A complex network model for the spread of Dutch Elm Disease in an urban forest is formulated. Ame... more A complex network model for the spread of Dutch Elm Disease in an urban forest is formulated. American elms are the focus of the model. Each elm can be in one of five states, a combination of their life and epidemiological status. Each tree is also potentially a host to a population of elm bark beetles, the vectors of Dutch Elm Disease. The epidemiological dynamics of trees is governed by a stochastic process that takes into account the dispersal of spore-carrying beetles between trees and potential contacts between tree root systems. The model describes seasonal variations of beetle activity and population dynamics. Numerical simulations and sensitivity analyses of the model are carried out. In this introductory paper, we use data from the City of Winnipeg, where Dutch Elm Disease is prevalent, and focus on two neighbourhoods representative of a residential area and an area with urban parks.

Research paper thumbnail of Intermediate filament dynamics: Disassembly regulation

Intermediate filament dynamics: Disassembly regulation

International Journal of Biomathematics, 2017

A mechanism of intermediate filament disassembly regulation is proposed in which disassembly is r... more A mechanism of intermediate filament disassembly regulation is proposed in which disassembly is regulated by the amount of proteins assembled in networks. It is also hypothesized that a delay might exist between regulation and actual disassembly. Under realistic biological conditions of assembly and disassembly, it is shown that such a delay is harmless and does not destabilize the organization of intermediate filaments in networks. However, for high rates of disassembly, the model predicts that delay can destabilize the organization, with the intermediate filament material oscillating between organizations mainly in networks and in nonfilamentous particles.

Research paper thumbnail of Biological modelling / Biomodélisation Intermediate filament net works: in vitro and in vivo assembly models

We propose two systems of ordinary differential equations modeling the assembly of intermediate f... more We propose two systems of ordinary differential equations modeling the assembly of intermediate filament networks. The first one describes the in vitro intermediate filament assembly dynamics. The second one deals with the in vivo evolution of cytokeratin, which is the intermediate filament protein expressed by epithelial cells. The in vitro model is then briefly analyzed

Research paper thumbnail of Epidemiological implications of mobility between a large urban centre and smaller satellite cities

Journal of Mathematical Biology, 2015

An SIR infectious disease propagation model is considered that incorporates mobility of individua... more An SIR infectious disease propagation model is considered that incorporates mobility of individuals between a large urban centre and smaller satellite cities. Because of the difference in population sizes, the urban centre has standard incidence and satellite cities have mass action incidence. It is shown that the general basic reproduction number R 0 acts as a threshold between global asymptotic stability of the disease free equilibrium and disease persistence. The case of Winnipeg (MB, Canada) and some neighbouring satellite communities is then considered numerically to complement the mathematical analysis, highlighting the importance of taking into account not only R 0 but also other measures of disease severity. It is found that the large urban centre governs most of the behaviour of the general system and control of the spread is better achieved by targeting it rather than reducing movement between the units. Also, the capacity of a satellite city to affect the general system depends on its population size and its connectivity to the main urban centre.

Research paper thumbnail of The effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7

The FASEB Journal, 2001

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent ce... more Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. We hypothesized that the integration of environmental factors might induce specific cytoskeletal architecture patterns, characterized by quantitative image analysis. Human breast cancer cells MCF-7, flown in space in a photon capsule, were fixed after 1.5, 22, and 48 h in orbit. Cells subjected to weightlessness were compared with 1g in-flight and ground controls. Postflight, fluorescent labelings were performed to visualize cell proliferation (Ki-67), signal transduction (phosphotyrosine), three cytoskeleton components (microtubules, microfilaments, and intermediate filaments), and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network, and chromatin structure. In weightlessness, phosphotyrosine signal transduction was lower, more cells were cycling, and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade. Microtubules were altered in many cells. The perinuclear cytokeratin network was more loosely 'woven', and chromatin structure was modified. The prolongaion of mitosis can be explained by an alteration of microtubule self-organization in weightlessness, involving reaction-diffusion processes. The loosening of the perinuclear cytokeratin network and modification of chromatin distribution are in agreement with basic predictions of cellular tensegrity. Key words: microgravity • image analysis solid body of literature now shows that the cell genotype is not the only determinant of normal and pathological cell behavior. For instance, tumor cells bearing numerous genomic abnormalities can be induced to behave in a phenotypically normal manner in response to modification of their microenvironment (1, 2). Therefore, for a cell to function normally, not only does the genotype need to be intact to some extent, with correct replication A

Research paper thumbnail of Physical interpretation of microtubule self-organization in gravitational fields

Physical interpretation of microtubule self-organization in gravitational fields

Physics Letters A, 2005

... View Within Article. A single TB dimer has about 40e negative charges [13]. If only 10% of th... more ... View Within Article. A single TB dimer has about 40e negative charges [13]. If only 10% of this charge is unscreened by counterions, then qeff=4e and the Bjerrum length , with ε=80 for water, at room temperature, can reach about 15 nm. ...

Research paper thumbnail of Large amplitude spatial fluctuations in the boundary region of the Bose–Einstein condensate in the Gross–Pitaevskii régime

Physica A: Statistical Mechanics and its Applications, 2003

The Gross-Pitaevskii rà egime of a Bose-Einstein condensate is investigated using a fully non-lin... more The Gross-Pitaevskii rà egime of a Bose-Einstein condensate is investigated using a fully non-linear approach. The conÿning potential ÿrst adopted is that of a linear ramp. An inÿnite class of new analytical solutions of this linear ramp potential approximation to the Gross-Pitaevskii equation is found which are characterised by pronounced large-amplitude oscillations close to the boundary of the condensate. The limiting case within this class is a nodeless ground state which is known from recent investigations as an extension of the Thomas-Fermi approximation. We have found the energies of the oscillatory states to lie above the ground state energy but recent experimental work, especially on spatially conÿned superconductors, indicates that such states may be easily occupied and made manifest at ÿnite temperatures. We have also investigated their stability using a Poincarà e section analysis as well as a linear perturbation approach. Both these techniques demonstrate stability against small perturbations. Finally, we have discussed the relevance of these quasi-one-dimensional solutions in the context of the fully three-dimensional condensates. This has been argued on the basis of numerical work and asymptotic approximations.

Research paper thumbnail of Nonlinear assembly kinetics and mechanical properties of biopolymers

Nonlinear Analysis: Theory, Methods & Applications, 2005

This paper discusses the role of nonlinearities in the physical description of key biomolecules t... more This paper discusses the role of nonlinearities in the physical description of key biomolecules that participate in crucial subcellular processes, namely actin, microtubules and ions crowding around these filaments. The assembly kinetics of actin is that of a nonlinear process that is governed by coupled nonlinear equations involving monomer concentration and filament number as the dynamical variables. The dendritic growth of actin networks in cell motility phenomena is described by the coupling of actin filaments to the protein Arp2/3. We then discuss how coupled differential equations describing the interactions between ions in solution and the filament they surround can lead to solitonic signal transmission. We also investigate the role of nonlinear dynamics in the formation of microtubules. Space-flight laboratory experiments have shown that the self-organization of microtubules is sensitive to gravitational conditions. We propose a model of self-organization of microtubules in a gravitational field based on the dominant chemical kinetics. The pattern formation of microtubule concentration is obtained in terms of a moving kink. Finally, we present a model of elastic properties of microtubules describing a microtubule as an elastic rod. We found that when the microtubule

Research paper thumbnail of Simulating the formation of keratin filament networks by a piecewise-deterministic Markov process

Journal of Theoretical Biology, 2009

Keratin intermediate filament networks are part of the cytoskeleton in epithelial cells. They wer... more Keratin intermediate filament networks are part of the cytoskeleton in epithelial cells. They were found to regulate viscoelastic properties and motility of cancer cells. Due to unique biochemical properties of keratin polymers, the knowledge of the mechanisms controlling keratin network formation is incomplete. A combination of deterministic and stochastic modeling techniques can be a valuable source of information since they can describe known mechanisms of network evolution while reflecting the uncertainty with respect to a variety of molecular events. We applied the concept of * These authors contributed equally. † corresponding author A c c e p t e d m a n u s c r i p t Simulating the formation of keratin filament networks by a PDMP piecewise-deterministic Markov processes to the modeling of keratin network formation in high spatiotemporal resolution. The deterministic component describes the diffusion-driven evolution of a pool of soluble keratin filament precursors fueling various network formation processes. Instants of network formation events are determined by a stochastic point process on the time axis. A probability distribution controlled by model parameters exercises control over the frequency of different mechanisms of network formation to be triggered. Locations of the network formation events are assigned dependent on the spatial distribution of the soluble pool of filament precursors. Based on this modeling approach, simulation studies revealed that the architecture of keratin networks mostly depends on the balance between filament elongation and branching processes. The spatial distribution of network mesh size, which strongly influences the mechanical characteristics of filament networks, mostly depends on lateral annealing processes. This mechanism which is a specific feature of intermediate filament networks appears to be a major and fast regulator of cell mechanics.

Research paper thumbnail of Propagation of Localized Bending Deformations in Microtubules

Journal of Computational and Theoretical Nanoscience, 2009

At a macroscopic level of large bending motions, a continuum medium model is proposed describing ... more At a macroscopic level of large bending motions, a continuum medium model is proposed describing a microtubule as an elastic rod. Compressional and shear deformations are excluded as less relevant biophysically. When the microtubule is subjected to a constant bending force, it is found that the dynamics of the angular deviation, with respect to the rectilinear configuration of the microtubule, is governed by a Sine-Gordon Equation. Particular analytical solutions of this equation are found which describe kink and anti-kink bending modes which may propagate at various subsonic speeds along the length of the microtubule. Kinetic energies of these modes are calculated for different propagation velocities and compared with thermal and ATP hydrolysis energies. Viscous damping is shown to be negligible for long microtubules and fast moving bending deformations.

Research paper thumbnail of Effect of pathogen-resistant vectors on the transmission dynamics of a vector-borne disease

Journal of Biological Dynamics, 2007

A model is introduced for the transmission dynamics of a vector-borne disease with two vector str... more A model is introduced for the transmission dynamics of a vector-borne disease with two vector strains, one wild and one pathogen-resistant; resistance comes at the cost of reduced reproductive fitness. The model, which assumes that vector reproduction can lead to the transmission or loss of resistance (reversion), is analyzed in a particular case with specified forms for the birth and force of infection functions. The vector component can have, in the absence of disease, a coexistence equilibrium where both strains survive. In the case where reversion is possible, this coexistence equilibrium is globally asymptotically stable when it exists. This equilibrium is still present in the full vector-host system, leading to a reduction of the associated reproduction number, thereby making elimination of the disease more feasible. When reversion is not possible, there can exist an additional equilibrium with only resistant vectors.

Research paper thumbnail of Anisotropic elastic properties of microtubules

The European Physical Journal E, 2005

We review and model the experimental parameters which characterize elastic properties of microtub... more We review and model the experimental parameters which characterize elastic properties of microtubules. Three macroscopic estimates are made of the anisotropic elastic moduli, accounting for the molecular forces between tubulin dimers: for a longitudinal compression of a microtubule, for a lateral force and for a shearing force. These estimates reflect the anisotropies in these parameters observed in several recent experiments.

Research paper thumbnail of Intermediate filament networks: in vitro and in vivo assembly models

Comptes Rendus Biologies, 2004

We propose two systems of ordinary differential equations modeling the assembly of intermediate f... more We propose two systems of ordinary differential equations modeling the assembly of intermediate filament networks. The first one describes the in vitro intermediate filament assembly dynamics. The second one deals with the in vivo evolution of cytokeratin, which is the intermediate filament protein expressed by epithelial cells. The in vitro model is then briefly analyzed in a simplified case. To cite this article: S.

Research paper thumbnail of Influence of the gravitational field on microtubule self-organization

Influence of the gravitational field on microtubule self-organization

Research paper thumbnail of Weightlessness acts on human breast cancer cell line MCF-7

Weightlessness acts on human breast cancer cell line MCF-7

Advances in Space Research, 2003

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent ce... more Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. Human breast cancer cells MCF-7, flown in space in a Photon capsule, were fixed after 1.5, 22 and 48 h in orbit. Cells subjected to weightlessness were compared to 1 g in-flight and ground controls. Post-flight, fluorescent labeling was performed to visualize cell proliferation (Ki-67), three cytoskeleton components and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network and chromatin structure. Several main phenomena were observed in weightlessness: The perinuclear cytokeratin network and chromatin structure were looser; More cells were cycling and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade; Microtubules were altered in many cells. The results reported in the first point are in agreement with basic predictions of cellular tensegrity. The prolongation of mitosis can be explained by an alteration of microtubules. We discuss here the different mechanisms involved in weightlessness alteration of microtubules: i) alteration of their self-organization by reaction-diffusion processes, and a mathematical model is proposed, ii) activation or deactivation of microtubules stabilizing proteins, acting on both microtubule and microfilament networks in cell cortex.

Research paper thumbnail of Dual-wavelength stopped-flow analysis of the lateral and longitudinal assembly kinetics of vimentin

Vimentin is a highly charged intermediate filament protein that inherently forms extended dimeric... more Vimentin is a highly charged intermediate filament protein that inherently forms extended dimeric coiled-coils, which serve as the basic building blocks of intermediate filaments. Under low ionic strength conditions, vimentin filaments dissociate into uniform tetrameric complexes of two anti-parallel oriented, half-staggered coiled-coil dimers. By addition of salt, vimentin tetramers spontaneously reassemble into filaments in a time-dependent process: i) lateral assembly of tetramers into unit-length filaments (ULFs); ii) longitudinal annealing of ULFs; iii) longitudinal assembly of filaments coupled with subsequent radial compaction. To independently determine the lateral and longitudinal assembly kinetics, we measure with a stopped-flow instrument the static light scattering signal at two different wavelengths (405 and 594 nm) with a temporal resolution of 3 ms, and analyze the signals based on Rayleigh-Gans theory. This theory considers that the intensity of the scattered light d...

Research paper thumbnail of Models of Vimentin Organization Under Actin-Driven Transport

arXiv (Cornell University), Sep 6, 2022

Intermediate filaments form an essential structural network, spread throughout the cytoplasm and ... more Intermediate filaments form an essential structural network, spread throughout the cytoplasm and play a key role in cell mechanics, intracellular organization and molecular signaling. The maintenance of the network and its adaptation to the cell's dynamic behavior relies on several mechanisms implicating cytoskeletal crosstalk which are not fully understood. Mathematical modeling allows us to compare several biologically realistic scenarios to help us interpret experimental data. In this study, we observe and model the dynamics of the vimentin intermediate filaments in single glial cells seeded on circular micropatterns following microtubule disruption by nocodazole treatment. In these conditions, the vimentin filaments move towards the cell center and accumulate before eventually reaching a steady-state. In absence of microtubule-driven transport, the motion of the vimentin network is primarily driven by actin-related mechanisms. To model these experimental findings, we hypothesize that vimentin may exist in two states, mobile and immobile, and switches between the states at unknown (either constant or non-constant) rates. Mobile vimentin are assumed to advect with either constant or non-constant velocity. We introduce several biologically realistic scenarios using this set of assumptions. For each scenario, we use differential evolution to find the best parameter sets resulting in a solution that most closely matches the experimental data, then the assumptions are evaluated using the Akaike Information Criterion. This modeling approach allows us to conclude that our experimental data are best explained by a spatially dependent trapping of intermediate filaments or a spatially dependent speed of actin-dependent transport.

Research paper thumbnail of Quarantine and the risk of COVID-19 importation

Epidemiology and Infection, Dec 9, 2020

Using a stochastic model, we assess the risk of importation-induced local transmission chains in ... more Using a stochastic model, we assess the risk of importation-induced local transmission chains in locations seeing few or no local transmissions and evaluate the role of quarantine in the mitigation of this risk. We find that the rate of importations plays a critical role in determining the risk that case importations lead to local transmission chains, more so than local transmission characteristics, i.e. strength of social distancing measures (NPI). The latter influences the severity of the outbreaks when they do take place. Quarantine after arrival in a location is an efficacious way to reduce the rate of importations. Locations that see no or low-level local transmission should ensure that the rate of importations remains low. A high level of compliance with post-arrival quarantine followed by testing achieves this objective with less of an impact than travel restrictions or bans.

Research paper thumbnail of Epidemiological implications of mobility between a large urban centre and smaller satellite cities

Journal of Mathematical Biology, Jan 14, 2015

An SIR infectious disease propagation model is considered that incorporates mobility of individua... more An SIR infectious disease propagation model is considered that incorporates mobility of individuals between a large urban centre and smaller satellite cities. Because of the difference in population sizes, the urban centre has standard incidence and satellite cities have mass action incidence. It is shown that the general basic reproduction number R 0 acts as a threshold between global asymptotic stability of the disease free equilibrium and disease persistence. The case of Winnipeg (MB, Canada) and some neighbouring satellite communities is then considered numerically to complement the mathematical analysis, highlighting the importance of taking into account not only R 0 but also other measures of disease severity. It is found that the large urban centre governs most of the behaviour of the general system and control of the spread is better achieved by targeting it rather than reducing movement between the units. Also, the capacity of a satellite city to affect the general system depends on its population size and its connectivity to the main urban centre.

Research paper thumbnail of Using Fluorescence Recovery After Photobleaching data to uncover filament dynamics

PLOS Computational Biology

Fluorescence Recovery After Photobleaching (FRAP) has been extensively used to understand molecul... more Fluorescence Recovery After Photobleaching (FRAP) has been extensively used to understand molecular dynamics in cells. This technique when applied to soluble, globular molecules driven by diffusion is easily interpreted and well understood. However, the classical methods of analysis cannot be applied to anisotropic structures subjected to directed transport, such as cytoskeletal filaments or elongated organelles transported along microtubule tracks. A new mathematical approach is needed to analyze FRAP data in this context and determine what information can be obtain from such experiments. To address these questions, we analyze fluorescence intensity profile curves after photobleaching of fluorescently labelled intermediate filaments anterogradely transported along microtubules. We apply the analysis to intermediate filament data to determine information about the filament motion. Our analysis consists of deriving equations for fluorescence intensity profiles and developing a mathem...

Research paper thumbnail of Spread of Dutch elm disease in an urban forest

Ecological Modelling, 2020

A complex network model for the spread of Dutch Elm Disease in an urban forest is formulated. Ame... more A complex network model for the spread of Dutch Elm Disease in an urban forest is formulated. American elms are the focus of the model. Each elm can be in one of five states, a combination of their life and epidemiological status. Each tree is also potentially a host to a population of elm bark beetles, the vectors of Dutch Elm Disease. The epidemiological dynamics of trees is governed by a stochastic process that takes into account the dispersal of spore-carrying beetles between trees and potential contacts between tree root systems. The model describes seasonal variations of beetle activity and population dynamics. Numerical simulations and sensitivity analyses of the model are carried out. In this introductory paper, we use data from the City of Winnipeg, where Dutch Elm Disease is prevalent, and focus on two neighbourhoods representative of a residential area and an area with urban parks.

Research paper thumbnail of Intermediate filament dynamics: Disassembly regulation

Intermediate filament dynamics: Disassembly regulation

International Journal of Biomathematics, 2017

A mechanism of intermediate filament disassembly regulation is proposed in which disassembly is r... more A mechanism of intermediate filament disassembly regulation is proposed in which disassembly is regulated by the amount of proteins assembled in networks. It is also hypothesized that a delay might exist between regulation and actual disassembly. Under realistic biological conditions of assembly and disassembly, it is shown that such a delay is harmless and does not destabilize the organization of intermediate filaments in networks. However, for high rates of disassembly, the model predicts that delay can destabilize the organization, with the intermediate filament material oscillating between organizations mainly in networks and in nonfilamentous particles.

Research paper thumbnail of Biological modelling / Biomodélisation Intermediate filament net works: in vitro and in vivo assembly models

We propose two systems of ordinary differential equations modeling the assembly of intermediate f... more We propose two systems of ordinary differential equations modeling the assembly of intermediate filament networks. The first one describes the in vitro intermediate filament assembly dynamics. The second one deals with the in vivo evolution of cytokeratin, which is the intermediate filament protein expressed by epithelial cells. The in vitro model is then briefly analyzed

Research paper thumbnail of Epidemiological implications of mobility between a large urban centre and smaller satellite cities

Journal of Mathematical Biology, 2015

An SIR infectious disease propagation model is considered that incorporates mobility of individua... more An SIR infectious disease propagation model is considered that incorporates mobility of individuals between a large urban centre and smaller satellite cities. Because of the difference in population sizes, the urban centre has standard incidence and satellite cities have mass action incidence. It is shown that the general basic reproduction number R 0 acts as a threshold between global asymptotic stability of the disease free equilibrium and disease persistence. The case of Winnipeg (MB, Canada) and some neighbouring satellite communities is then considered numerically to complement the mathematical analysis, highlighting the importance of taking into account not only R 0 but also other measures of disease severity. It is found that the large urban centre governs most of the behaviour of the general system and control of the spread is better achieved by targeting it rather than reducing movement between the units. Also, the capacity of a satellite city to affect the general system depends on its population size and its connectivity to the main urban centre.

Research paper thumbnail of The effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7

The FASEB Journal, 2001

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent ce... more Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. We hypothesized that the integration of environmental factors might induce specific cytoskeletal architecture patterns, characterized by quantitative image analysis. Human breast cancer cells MCF-7, flown in space in a photon capsule, were fixed after 1.5, 22, and 48 h in orbit. Cells subjected to weightlessness were compared with 1g in-flight and ground controls. Postflight, fluorescent labelings were performed to visualize cell proliferation (Ki-67), signal transduction (phosphotyrosine), three cytoskeleton components (microtubules, microfilaments, and intermediate filaments), and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network, and chromatin structure. In weightlessness, phosphotyrosine signal transduction was lower, more cells were cycling, and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade. Microtubules were altered in many cells. The perinuclear cytokeratin network was more loosely 'woven', and chromatin structure was modified. The prolongaion of mitosis can be explained by an alteration of microtubule self-organization in weightlessness, involving reaction-diffusion processes. The loosening of the perinuclear cytokeratin network and modification of chromatin distribution are in agreement with basic predictions of cellular tensegrity. Key words: microgravity • image analysis solid body of literature now shows that the cell genotype is not the only determinant of normal and pathological cell behavior. For instance, tumor cells bearing numerous genomic abnormalities can be induced to behave in a phenotypically normal manner in response to modification of their microenvironment (1, 2). Therefore, for a cell to function normally, not only does the genotype need to be intact to some extent, with correct replication A

Research paper thumbnail of Physical interpretation of microtubule self-organization in gravitational fields

Physical interpretation of microtubule self-organization in gravitational fields

Physics Letters A, 2005

... View Within Article. A single TB dimer has about 40e negative charges [13]. If only 10% of th... more ... View Within Article. A single TB dimer has about 40e negative charges [13]. If only 10% of this charge is unscreened by counterions, then qeff=4e and the Bjerrum length , with ε=80 for water, at room temperature, can reach about 15 nm. ...

Research paper thumbnail of Large amplitude spatial fluctuations in the boundary region of the Bose–Einstein condensate in the Gross–Pitaevskii régime

Physica A: Statistical Mechanics and its Applications, 2003

The Gross-Pitaevskii rà egime of a Bose-Einstein condensate is investigated using a fully non-lin... more The Gross-Pitaevskii rà egime of a Bose-Einstein condensate is investigated using a fully non-linear approach. The conÿning potential ÿrst adopted is that of a linear ramp. An inÿnite class of new analytical solutions of this linear ramp potential approximation to the Gross-Pitaevskii equation is found which are characterised by pronounced large-amplitude oscillations close to the boundary of the condensate. The limiting case within this class is a nodeless ground state which is known from recent investigations as an extension of the Thomas-Fermi approximation. We have found the energies of the oscillatory states to lie above the ground state energy but recent experimental work, especially on spatially conÿned superconductors, indicates that such states may be easily occupied and made manifest at ÿnite temperatures. We have also investigated their stability using a Poincarà e section analysis as well as a linear perturbation approach. Both these techniques demonstrate stability against small perturbations. Finally, we have discussed the relevance of these quasi-one-dimensional solutions in the context of the fully three-dimensional condensates. This has been argued on the basis of numerical work and asymptotic approximations.

Research paper thumbnail of Nonlinear assembly kinetics and mechanical properties of biopolymers

Nonlinear Analysis: Theory, Methods & Applications, 2005

This paper discusses the role of nonlinearities in the physical description of key biomolecules t... more This paper discusses the role of nonlinearities in the physical description of key biomolecules that participate in crucial subcellular processes, namely actin, microtubules and ions crowding around these filaments. The assembly kinetics of actin is that of a nonlinear process that is governed by coupled nonlinear equations involving monomer concentration and filament number as the dynamical variables. The dendritic growth of actin networks in cell motility phenomena is described by the coupling of actin filaments to the protein Arp2/3. We then discuss how coupled differential equations describing the interactions between ions in solution and the filament they surround can lead to solitonic signal transmission. We also investigate the role of nonlinear dynamics in the formation of microtubules. Space-flight laboratory experiments have shown that the self-organization of microtubules is sensitive to gravitational conditions. We propose a model of self-organization of microtubules in a gravitational field based on the dominant chemical kinetics. The pattern formation of microtubule concentration is obtained in terms of a moving kink. Finally, we present a model of elastic properties of microtubules describing a microtubule as an elastic rod. We found that when the microtubule

Research paper thumbnail of Simulating the formation of keratin filament networks by a piecewise-deterministic Markov process

Journal of Theoretical Biology, 2009

Keratin intermediate filament networks are part of the cytoskeleton in epithelial cells. They wer... more Keratin intermediate filament networks are part of the cytoskeleton in epithelial cells. They were found to regulate viscoelastic properties and motility of cancer cells. Due to unique biochemical properties of keratin polymers, the knowledge of the mechanisms controlling keratin network formation is incomplete. A combination of deterministic and stochastic modeling techniques can be a valuable source of information since they can describe known mechanisms of network evolution while reflecting the uncertainty with respect to a variety of molecular events. We applied the concept of * These authors contributed equally. † corresponding author A c c e p t e d m a n u s c r i p t Simulating the formation of keratin filament networks by a PDMP piecewise-deterministic Markov processes to the modeling of keratin network formation in high spatiotemporal resolution. The deterministic component describes the diffusion-driven evolution of a pool of soluble keratin filament precursors fueling various network formation processes. Instants of network formation events are determined by a stochastic point process on the time axis. A probability distribution controlled by model parameters exercises control over the frequency of different mechanisms of network formation to be triggered. Locations of the network formation events are assigned dependent on the spatial distribution of the soluble pool of filament precursors. Based on this modeling approach, simulation studies revealed that the architecture of keratin networks mostly depends on the balance between filament elongation and branching processes. The spatial distribution of network mesh size, which strongly influences the mechanical characteristics of filament networks, mostly depends on lateral annealing processes. This mechanism which is a specific feature of intermediate filament networks appears to be a major and fast regulator of cell mechanics.

Research paper thumbnail of Propagation of Localized Bending Deformations in Microtubules

Journal of Computational and Theoretical Nanoscience, 2009

At a macroscopic level of large bending motions, a continuum medium model is proposed describing ... more At a macroscopic level of large bending motions, a continuum medium model is proposed describing a microtubule as an elastic rod. Compressional and shear deformations are excluded as less relevant biophysically. When the microtubule is subjected to a constant bending force, it is found that the dynamics of the angular deviation, with respect to the rectilinear configuration of the microtubule, is governed by a Sine-Gordon Equation. Particular analytical solutions of this equation are found which describe kink and anti-kink bending modes which may propagate at various subsonic speeds along the length of the microtubule. Kinetic energies of these modes are calculated for different propagation velocities and compared with thermal and ATP hydrolysis energies. Viscous damping is shown to be negligible for long microtubules and fast moving bending deformations.

Research paper thumbnail of Effect of pathogen-resistant vectors on the transmission dynamics of a vector-borne disease

Journal of Biological Dynamics, 2007

A model is introduced for the transmission dynamics of a vector-borne disease with two vector str... more A model is introduced for the transmission dynamics of a vector-borne disease with two vector strains, one wild and one pathogen-resistant; resistance comes at the cost of reduced reproductive fitness. The model, which assumes that vector reproduction can lead to the transmission or loss of resistance (reversion), is analyzed in a particular case with specified forms for the birth and force of infection functions. The vector component can have, in the absence of disease, a coexistence equilibrium where both strains survive. In the case where reversion is possible, this coexistence equilibrium is globally asymptotically stable when it exists. This equilibrium is still present in the full vector-host system, leading to a reduction of the associated reproduction number, thereby making elimination of the disease more feasible. When reversion is not possible, there can exist an additional equilibrium with only resistant vectors.

Research paper thumbnail of Anisotropic elastic properties of microtubules

The European Physical Journal E, 2005

We review and model the experimental parameters which characterize elastic properties of microtub... more We review and model the experimental parameters which characterize elastic properties of microtubules. Three macroscopic estimates are made of the anisotropic elastic moduli, accounting for the molecular forces between tubulin dimers: for a longitudinal compression of a microtubule, for a lateral force and for a shearing force. These estimates reflect the anisotropies in these parameters observed in several recent experiments.

Research paper thumbnail of Intermediate filament networks: in vitro and in vivo assembly models

Comptes Rendus Biologies, 2004

We propose two systems of ordinary differential equations modeling the assembly of intermediate f... more We propose two systems of ordinary differential equations modeling the assembly of intermediate filament networks. The first one describes the in vitro intermediate filament assembly dynamics. The second one deals with the in vivo evolution of cytokeratin, which is the intermediate filament protein expressed by epithelial cells. The in vitro model is then briefly analyzed in a simplified case. To cite this article: S.

Research paper thumbnail of Influence of the gravitational field on microtubule self-organization

Influence of the gravitational field on microtubule self-organization

Research paper thumbnail of Weightlessness acts on human breast cancer cell line MCF-7

Weightlessness acts on human breast cancer cell line MCF-7

Advances in Space Research, 2003

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent ce... more Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. Human breast cancer cells MCF-7, flown in space in a Photon capsule, were fixed after 1.5, 22 and 48 h in orbit. Cells subjected to weightlessness were compared to 1 g in-flight and ground controls. Post-flight, fluorescent labeling was performed to visualize cell proliferation (Ki-67), three cytoskeleton components and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network and chromatin structure. Several main phenomena were observed in weightlessness: The perinuclear cytokeratin network and chromatin structure were looser; More cells were cycling and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade; Microtubules were altered in many cells. The results reported in the first point are in agreement with basic predictions of cellular tensegrity. The prolongation of mitosis can be explained by an alteration of microtubules. We discuss here the different mechanisms involved in weightlessness alteration of microtubules: i) alteration of their self-organization by reaction-diffusion processes, and a mathematical model is proposed, ii) activation or deactivation of microtubules stabilizing proteins, acting on both microtubule and microfilament networks in cell cortex.