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

Papers by Stephanie Portet

Research paper thumbnail of Impact of noise on the regulation of intracellular transport of intermediate filaments

Journal of Theoretical Biology

Noise affects all biological processes from molecules to cells, organisms and populations. Althou... more Noise affects all biological processes from molecules to cells, organisms and populations. Although the effect of noise on these processes is highly variable, evidence is accumulating which shows natural stochastic fluctuations (noise) can facilitate biological functions. Herein, we investigate the effect of noise on the transport of intermediate filaments in cells by comparing the stochastic and deterministic formalizations of the bidirectional transport of intermediate filaments, long elastic polymers transported along microtubules by antagonistic motor proteins [1, 2]. By numerically exploring discrepancies in timescales and attractors between both formalizations, we characterize the impact of stochastic fluctuations on the individual and ensemble transport. Biologically, we find that noise promotes the collective movement of intermediate filaments and increases the efficiency of its regulation by the biochemical properties of motor-cargo interactions. While stochastic fluctuations reduce the impact of the initial distributions of motor proteins in cells, the number of binding sites and the affinity of motor-cargo interactions are the key parameters controlling transport efficiency and efficacy.

Research paper thumbnail of A primer on model selection using the Akaike Information Criterion

Infectious Disease Modelling, 2020

A powerful investigative tool in biology is to consider not a single mathematical model but a col... more A powerful investigative tool in biology is to consider not a single mathematical model but a collection of models designed to explore different working hypotheses and select the best model in that collection. In these lecture notes, the usual workflow of the use of mathematical models to investigate a biological problem is described and the use of a collection of model is motivated. Models depend on parameters that must be estimated using observations; and when a collection of models is considered, the best model has then to be identified based on available observations. Hence, model calibration and selection, which are intrinsically linked, are essential steps of the workflow. Here, some procedures for model calibration and a criterion, the Akaike Information Criterion, of model selection based on experimental data are described. Rough derivation, practical technique of computation and use of this criterion are detailed.

Research paper thumbnail of Mathematical modelling of OAS2 activation by dsRNA and effects of dsRNA lengths

Research paper thumbnail of A mathematical analysis of an activator-inhibitor Rho GTPase model

Journal of Computational Dynamics, 2021

Recent experimental observations reveal that local cellular contraction pulses emerge via a combi... more Recent experimental observations reveal that local cellular contraction pulses emerge via a combination of fast positive and slow negative feedbacks based on a signal network composed of Rho, GEF and Myosin interactions [22]. As an examplary, we propose to study a plausible, hypothetical temporal model that mirrors general principles of fast positive and slow negative feedback, a hallmark for activator-inhibitor models. The methodology involves (ⅰ) a qualitative analysis to unravel system switching between different states (stable, excitable, oscillatory and bistable) through model parameter variations; (ⅱ) a numerical bifurcation analysis using the positive feedback mediator concentration as a bifurcation parameter, (ⅲ) a sensitivity analysis to quantify the effect of parameter uncertainty on the model output for different dynamic regimes of the model system; and (ⅳ) numerical simulations of the model system for model predictions. Our methodological approach supports the role of ma...

Research paper thumbnail of Risk of COVID-19 variant importation – How useful are travel control measures?

Infectious Disease Modelling, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network

Cell Reports, 2020

Leif (2020) Optogenetic tuning reveals rho amplificationdependent dynamics of a cell contraction ... more Leif (2020) Optogenetic tuning reveals rho amplificationdependent dynamics of a cell contraction signal network. Cell Rep, 33 (9). a108467 1-14.

Research paper thumbnail of Assessing the risk of COVID-19 importation and the effect of quarantine

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Research paper thumbnail of A simple model for COVID-19

Infectious Disease Modelling, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Research paper thumbnail of Deciphering the transport of elastic filaments by antagonistic motor proteins

Physical Review E, 2019

Intermediate filaments are long elastic fibers that are transported by the microtubule-associated... more Intermediate filaments are long elastic fibers that are transported by the microtubule-associated motor proteins kinesin and dynein inside the cell. How elastic filaments are efficiently transported by antagonistic motors is not well understood and is difficult to measure with current experimental techniques. Adapting the tug-of-war paradigm for vesiclelike cargos, we develop a mathematical model to describe the motion of an elastic filament punctually bound to antagonistic motors. As observed in cells, up to three modes of transport are obtained; dynein-driven retrograde, kinesin-driven anterograde fast motions, and a slow motion. Motor properties and initial conditions that depend on intracellular context regulate the transport of filaments. Filament elasticity is found to affect both the mode and the efficiency of transport. We further show that the coordination of motors along the filament emerges from the interplay between intracellular context and elastic properties of filaments.

Research paper thumbnail of A primer on model selection using the Akaike Information Criterion

Infectious Disease Modelling, 2020

A powerful investigative tool in biology is to consider not a single mathematical model but a col... more A powerful investigative tool in biology is to consider not a single mathematical model but a collection of models designed to explore different working hypotheses and select the best model in that collection. In these lecture notes, the usual workflow of the use of mathematical models to investigate a biological problem is described and the use of a collection of model is motivated. Models depend on parameters that must be estimated using observations; and when a collection of models is considered, the best model has then to be identified based on available observations. Hence, model calibration and selection, which are intrinsically linked, are essential steps of the workflow. Here, some procedures for model calibration and a criterion, the Akaike Information Criterion, of model selection based on experimental data are described. Rough derivation, practical technique of computation and use of this criterion are detailed.

Research paper thumbnail of Stochastic modeling reveals how motor protein and filament properties affect intermediate filament transport

Journal of Theoretical Biology, 2018

Intermediate filaments are a key component of the cytoskeleton. Their transport along microtubule... more Intermediate filaments are a key component of the cytoskeleton. Their transport along microtubules plays an essential role in the control of the shape and structural organization of cells. To identify the key parameters responsible for the control of intermediate filament transport, we generated a model of elastic filament transport by microtubule-associated dynein and kinesin. The model is also applicable to the transport of any elastically-coupled cargoes. We investigate the effect of filament properties such as number of motor binding sites, length, and elasticity on motion of filaments. Additionally, we consider the effect of motor properties, i.e. off rates, on filament transport. When one motor has a catch bond off rate it dictates the motion, whereas when motors have the same type of off rate filaments can alternate between retrograde and anterograde motions. The elasticity of filaments optimizes the filament transport and the coordination of motors along the length of the filament.

Research paper thumbnail of Models of spatial and orientational self-organization of microtubules under the influence of gravitational fields

Physical Review E, 2003

͑2000͔͒ showed that the self-organization of microtubules from purified tubulin solutions is sens... more ͑2000͔͒ showed that the self-organization of microtubules from purified tubulin solutions is sensitive to gravitational conditions. In this paper, we propose two models of spatial and orientational self-organization of microtubules in a gravitational field. First, the spatial model is based on the dominant chemical kinetics. The pattern formation of microtubule concentration is obtained ͑1͒ in terms of a moving kink in the limit when the disassembly rate is negligible, and ͑2͒ for the case of no free tubulin and only assembled microtubules present. Second, the orientational pattern of striped microtubule domains is consistent with predictions from a phenomenological Landau-Ginzburg free energy expansion in terms of an orientational order parameter.

Research paper thumbnail of Keratin Dynamics: Modeling the Interplay between Turnover and Transport

PloS one, 2015

Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin networ... more Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin network in cells are shaped by their dynamical organization. Using a collection of experimentally-driven mathematical models, different hypotheses for the turnover and transport of the keratin material in epithelial cells are tested. The interplay between turnover and transport and their effects on the keratin organization in cells are hence investigated by combining mathematical modeling and experimental data. Amongst the collection of mathematical models considered, a best model strongly supported by experimental data is identified. Fundamental to this approach is the fact that optimal parameter values associated with the best fit for each model are established. The best candidate among the best fits is characterized by the disassembly of the assembled keratin material in the perinuclear region and an active transport of the assembled keratin. Our study shows that an active transport of the ...

Research paper thumbnail of Editorial: proceedings of The Second International Conference of the French-speaking Society for Theoretical Biology

Acta biotheoretica, 2009

These meeting are still held in years where the International Conference is not taking place. Dur... more These meeting are still held in years where the International Conference is not taking place. During the Annual Meetings and the International Conferences, the participation of students is emphasized by the attribution of a prize for best student poster and/or presentation. In Winnipeg, the René Thom prize was awarded for the first time (Thom was a founding member of SFBT). Recipients of the prize were Virginie LeRolle (best presentation) and Peng T. (Troy) Teo (best poster). The range of topics discussed during SFBT events is quite broad, covering many aspects of theoretical biology ranging from complex mathematical and physical problems to philosophical considerations. The articles published in this special issue serve to illustrate this diversity. Jacques Demongeot considers the notion of biological age, which he opposes to the notion of chronological age. He argues that the number of divisions that a cell has undergone and can still undergo is better suited for the description of cell age, but also of organ age, and presents applications of this notion in various contexts. Alexander Dibrov et al's contribution deals with a problem of computational chemistry in the Life Sciences. They propose a new method to rank protein-protein interaction models using free energy minimization and present a rational method for

Research paper thumbnail of Impact of viral mutation on suppression of infection by cytotoxic T lymphocytes

ABSTRACT We develop a deterministic model describing the dynamics of infected cells wearing nnn e... more ABSTRACT We develop a deterministic model describing the dynamics of infected cells wearing nnn epitopes recognizable by nnn CTL clones, in which mutation can lead to the epitopes becoming unrecognizable by their cognate CTL clone. Some mathematical and computational analyses of the resulting large scale system of 2n+n2^n+n2n+n equations are conducted. The model is used to examine the ability of CTL response to suppress infection in the presence of mutations. Several situations in which CTL escape happens are identified and conditions in which infection is controlled are also derived. The influence of the probability of mutation is numerically investigated.

Research paper thumbnail of An <em>in vivo</em> intermediate filament assembly model

Mathematical Biosciences and Engineering, 2008

A model is developed to study the in vivo intermediate filament organization in terms of repartit... more A model is developed to study the in vivo intermediate filament organization in terms of repartition between four different structural states: soluble proteins, particles, short and long filaments. An analysis is conducted, showing that the system has a unique, globally asymptotically stable equilibrium. By means of sensitivity analysis, the influence of parameters on the system is studied. In agreement with biological observations, it is shown that post-translational modifications of intermediate filament proteins resulting in filament solubilization are the main regulators of the intermediate filament organization. A high signalling-dependent solubilization of filaments favours the intermediate filament aggregation in particles.

Research paper thumbnail of Organization of the cytokeratin network in an epithelial cell

Journal of Theoretical Biology, 2003

The cytoskeleton is a dynamic three-dimensional structure mainly located in the cytoplasm. It is ... more The cytoskeleton is a dynamic three-dimensional structure mainly located in the cytoplasm. It is involved in many cell functions such as mechanical signal transduction and maintenance of cell integrity. Among the three cytoskeletal components, intermediate filaments (the cytokeratin in epithelial cells) are the best candidates for this mechanical role. A model of the establishment of the cytokeratin network of an epithelial cell is proposed to study the dependence of its structural organization on extracellular mechanical environment. To implicitly describe the latter and its effects on the intracellular domain, we use mechanically regulated protein synthesis. Our model is a hybrid of a partial differential equation of parabolic type, governing the evolution of the concentration of cytokeratin, and a set of stochastic differential equations describing the dynamics of filaments. Each filament is described by a stochastic differential equation that reflects both the local interactions with the environment and the non-local interactions via the past history of the filament. A three-dimensional simulation model is derived from this mathematical model. This simulation model is then used to obtain examples of cytokeratin network architectures under given mechanical conditions, and to study the influence of several parameters.

Research paper thumbnail of Dynamics of in vitro intermediate filament length distributions

Journal of Theoretical Biology, 2013

An aggregation model with explicit expression of association rate constants is considered to stud... more An aggregation model with explicit expression of association rate constants is considered to study in vitro type III intermediate filament length distribution dynamics. Different assumptions on the properties of filaments and probability of aggregation are considered, leading to four models. Fitting of model responses to experimental data leads to the identification of the most appropriate model to represent each time point of the assembly. A combination of models allows the construction of a mixed model that represents well the complete assembly dynamics: it is found that the rate constants decrease with respect to filament size when the aggregation involves at least one short filament, whereas for longer filaments they are almost independent of size. The flexible nature of filaments is thus important in the assembly of intermediate filaments.

Research paper thumbnail of Gravitational Symmetry Breaking Leads to a Polar Liquid Crystal Phase of Microtubules In Vitro

Journal of Biological Physics, 2005

Recent space-flight experiments performed by Tabony's team provided further evidence that a micro... more Recent space-flight experiments performed by Tabony's team provided further evidence that a microgravity environment strongly affects the spatio-temporal organization of microtubule assemblies. Characteristic time and length scales were found that govern the organization of oriented bundles under Earth's gravitational field (GF). No such organization has been observed in a microgravity environment. This paper discusses physical mechanisms resulting in pattern formation under gravity and its disappearance in microgravity. The subtle interplay between chemical kinetics, diffusion, gravitational drift, thermal fluctuations, electrostatic interactions and liquid crystalline characteristics provides a plausible scenario.

Research paper thumbnail of A mathematical model for the keratin cycle of assembly and disassembly

IMA Journal of Applied Mathematics, 2013

We formulate a mathematical model to study the in vivo keratin organization in terms of repartiti... more We formulate a mathematical model to study the in vivo keratin organization in terms of repartition of the keratin material between three different structural states: soluble proteins, filament precursors and filamentous state. The model describes a cycle of assembly and disassembly of keratin material. A generic nucleation function and structural stability of filament precursors are assumed. It is established that the three structural states always coexist and that the repartition of keratin material never exhibits any cyclic behaviour. Under some conditions, it is shown that the choice of the nucleation function does not affect the qualitative behaviour of the system. However, it might change the stable repartition of the keratin material in the cell.

Research paper thumbnail of Impact of noise on the regulation of intracellular transport of intermediate filaments

Journal of Theoretical Biology

Noise affects all biological processes from molecules to cells, organisms and populations. Althou... more Noise affects all biological processes from molecules to cells, organisms and populations. Although the effect of noise on these processes is highly variable, evidence is accumulating which shows natural stochastic fluctuations (noise) can facilitate biological functions. Herein, we investigate the effect of noise on the transport of intermediate filaments in cells by comparing the stochastic and deterministic formalizations of the bidirectional transport of intermediate filaments, long elastic polymers transported along microtubules by antagonistic motor proteins [1, 2]. By numerically exploring discrepancies in timescales and attractors between both formalizations, we characterize the impact of stochastic fluctuations on the individual and ensemble transport. Biologically, we find that noise promotes the collective movement of intermediate filaments and increases the efficiency of its regulation by the biochemical properties of motor-cargo interactions. While stochastic fluctuations reduce the impact of the initial distributions of motor proteins in cells, the number of binding sites and the affinity of motor-cargo interactions are the key parameters controlling transport efficiency and efficacy.

Research paper thumbnail of A primer on model selection using the Akaike Information Criterion

Infectious Disease Modelling, 2020

A powerful investigative tool in biology is to consider not a single mathematical model but a col... more A powerful investigative tool in biology is to consider not a single mathematical model but a collection of models designed to explore different working hypotheses and select the best model in that collection. In these lecture notes, the usual workflow of the use of mathematical models to investigate a biological problem is described and the use of a collection of model is motivated. Models depend on parameters that must be estimated using observations; and when a collection of models is considered, the best model has then to be identified based on available observations. Hence, model calibration and selection, which are intrinsically linked, are essential steps of the workflow. Here, some procedures for model calibration and a criterion, the Akaike Information Criterion, of model selection based on experimental data are described. Rough derivation, practical technique of computation and use of this criterion are detailed.

Research paper thumbnail of Mathematical modelling of OAS2 activation by dsRNA and effects of dsRNA lengths

Research paper thumbnail of A mathematical analysis of an activator-inhibitor Rho GTPase model

Journal of Computational Dynamics, 2021

Recent experimental observations reveal that local cellular contraction pulses emerge via a combi... more Recent experimental observations reveal that local cellular contraction pulses emerge via a combination of fast positive and slow negative feedbacks based on a signal network composed of Rho, GEF and Myosin interactions [22]. As an examplary, we propose to study a plausible, hypothetical temporal model that mirrors general principles of fast positive and slow negative feedback, a hallmark for activator-inhibitor models. The methodology involves (ⅰ) a qualitative analysis to unravel system switching between different states (stable, excitable, oscillatory and bistable) through model parameter variations; (ⅱ) a numerical bifurcation analysis using the positive feedback mediator concentration as a bifurcation parameter, (ⅲ) a sensitivity analysis to quantify the effect of parameter uncertainty on the model output for different dynamic regimes of the model system; and (ⅳ) numerical simulations of the model system for model predictions. Our methodological approach supports the role of ma...

Research paper thumbnail of Risk of COVID-19 variant importation – How useful are travel control measures?

Infectious Disease Modelling, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network

Cell Reports, 2020

Leif (2020) Optogenetic tuning reveals rho amplificationdependent dynamics of a cell contraction ... more Leif (2020) Optogenetic tuning reveals rho amplificationdependent dynamics of a cell contraction signal network. Cell Rep, 33 (9). a108467 1-14.

Research paper thumbnail of Assessing the risk of COVID-19 importation and the effect of quarantine

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Research paper thumbnail of A simple model for COVID-19

Infectious Disease Modelling, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Research paper thumbnail of Deciphering the transport of elastic filaments by antagonistic motor proteins

Physical Review E, 2019

Intermediate filaments are long elastic fibers that are transported by the microtubule-associated... more Intermediate filaments are long elastic fibers that are transported by the microtubule-associated motor proteins kinesin and dynein inside the cell. How elastic filaments are efficiently transported by antagonistic motors is not well understood and is difficult to measure with current experimental techniques. Adapting the tug-of-war paradigm for vesiclelike cargos, we develop a mathematical model to describe the motion of an elastic filament punctually bound to antagonistic motors. As observed in cells, up to three modes of transport are obtained; dynein-driven retrograde, kinesin-driven anterograde fast motions, and a slow motion. Motor properties and initial conditions that depend on intracellular context regulate the transport of filaments. Filament elasticity is found to affect both the mode and the efficiency of transport. We further show that the coordination of motors along the filament emerges from the interplay between intracellular context and elastic properties of filaments.

Research paper thumbnail of A primer on model selection using the Akaike Information Criterion

Infectious Disease Modelling, 2020

A powerful investigative tool in biology is to consider not a single mathematical model but a col... more A powerful investigative tool in biology is to consider not a single mathematical model but a collection of models designed to explore different working hypotheses and select the best model in that collection. In these lecture notes, the usual workflow of the use of mathematical models to investigate a biological problem is described and the use of a collection of model is motivated. Models depend on parameters that must be estimated using observations; and when a collection of models is considered, the best model has then to be identified based on available observations. Hence, model calibration and selection, which are intrinsically linked, are essential steps of the workflow. Here, some procedures for model calibration and a criterion, the Akaike Information Criterion, of model selection based on experimental data are described. Rough derivation, practical technique of computation and use of this criterion are detailed.

Research paper thumbnail of Stochastic modeling reveals how motor protein and filament properties affect intermediate filament transport

Journal of Theoretical Biology, 2018

Intermediate filaments are a key component of the cytoskeleton. Their transport along microtubule... more Intermediate filaments are a key component of the cytoskeleton. Their transport along microtubules plays an essential role in the control of the shape and structural organization of cells. To identify the key parameters responsible for the control of intermediate filament transport, we generated a model of elastic filament transport by microtubule-associated dynein and kinesin. The model is also applicable to the transport of any elastically-coupled cargoes. We investigate the effect of filament properties such as number of motor binding sites, length, and elasticity on motion of filaments. Additionally, we consider the effect of motor properties, i.e. off rates, on filament transport. When one motor has a catch bond off rate it dictates the motion, whereas when motors have the same type of off rate filaments can alternate between retrograde and anterograde motions. The elasticity of filaments optimizes the filament transport and the coordination of motors along the length of the filament.

Research paper thumbnail of Models of spatial and orientational self-organization of microtubules under the influence of gravitational fields

Physical Review E, 2003

͑2000͔͒ showed that the self-organization of microtubules from purified tubulin solutions is sens... more ͑2000͔͒ showed that the self-organization of microtubules from purified tubulin solutions is sensitive to gravitational conditions. In this paper, we propose two models of spatial and orientational self-organization of microtubules in a gravitational field. First, the spatial model is based on the dominant chemical kinetics. The pattern formation of microtubule concentration is obtained ͑1͒ in terms of a moving kink in the limit when the disassembly rate is negligible, and ͑2͒ for the case of no free tubulin and only assembled microtubules present. Second, the orientational pattern of striped microtubule domains is consistent with predictions from a phenomenological Landau-Ginzburg free energy expansion in terms of an orientational order parameter.

Research paper thumbnail of Keratin Dynamics: Modeling the Interplay between Turnover and Transport

PloS one, 2015

Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin networ... more Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin network in cells are shaped by their dynamical organization. Using a collection of experimentally-driven mathematical models, different hypotheses for the turnover and transport of the keratin material in epithelial cells are tested. The interplay between turnover and transport and their effects on the keratin organization in cells are hence investigated by combining mathematical modeling and experimental data. Amongst the collection of mathematical models considered, a best model strongly supported by experimental data is identified. Fundamental to this approach is the fact that optimal parameter values associated with the best fit for each model are established. The best candidate among the best fits is characterized by the disassembly of the assembled keratin material in the perinuclear region and an active transport of the assembled keratin. Our study shows that an active transport of the ...

Research paper thumbnail of Editorial: proceedings of The Second International Conference of the French-speaking Society for Theoretical Biology

Acta biotheoretica, 2009

These meeting are still held in years where the International Conference is not taking place. Dur... more These meeting are still held in years where the International Conference is not taking place. During the Annual Meetings and the International Conferences, the participation of students is emphasized by the attribution of a prize for best student poster and/or presentation. In Winnipeg, the René Thom prize was awarded for the first time (Thom was a founding member of SFBT). Recipients of the prize were Virginie LeRolle (best presentation) and Peng T. (Troy) Teo (best poster). The range of topics discussed during SFBT events is quite broad, covering many aspects of theoretical biology ranging from complex mathematical and physical problems to philosophical considerations. The articles published in this special issue serve to illustrate this diversity. Jacques Demongeot considers the notion of biological age, which he opposes to the notion of chronological age. He argues that the number of divisions that a cell has undergone and can still undergo is better suited for the description of cell age, but also of organ age, and presents applications of this notion in various contexts. Alexander Dibrov et al's contribution deals with a problem of computational chemistry in the Life Sciences. They propose a new method to rank protein-protein interaction models using free energy minimization and present a rational method for

Research paper thumbnail of Impact of viral mutation on suppression of infection by cytotoxic T lymphocytes

ABSTRACT We develop a deterministic model describing the dynamics of infected cells wearing nnn e... more ABSTRACT We develop a deterministic model describing the dynamics of infected cells wearing nnn epitopes recognizable by nnn CTL clones, in which mutation can lead to the epitopes becoming unrecognizable by their cognate CTL clone. Some mathematical and computational analyses of the resulting large scale system of 2n+n2^n+n2n+n equations are conducted. The model is used to examine the ability of CTL response to suppress infection in the presence of mutations. Several situations in which CTL escape happens are identified and conditions in which infection is controlled are also derived. The influence of the probability of mutation is numerically investigated.

Research paper thumbnail of An <em>in vivo</em> intermediate filament assembly model

Mathematical Biosciences and Engineering, 2008

A model is developed to study the in vivo intermediate filament organization in terms of repartit... more A model is developed to study the in vivo intermediate filament organization in terms of repartition between four different structural states: soluble proteins, particles, short and long filaments. An analysis is conducted, showing that the system has a unique, globally asymptotically stable equilibrium. By means of sensitivity analysis, the influence of parameters on the system is studied. In agreement with biological observations, it is shown that post-translational modifications of intermediate filament proteins resulting in filament solubilization are the main regulators of the intermediate filament organization. A high signalling-dependent solubilization of filaments favours the intermediate filament aggregation in particles.

Research paper thumbnail of Organization of the cytokeratin network in an epithelial cell

Journal of Theoretical Biology, 2003

The cytoskeleton is a dynamic three-dimensional structure mainly located in the cytoplasm. It is ... more The cytoskeleton is a dynamic three-dimensional structure mainly located in the cytoplasm. It is involved in many cell functions such as mechanical signal transduction and maintenance of cell integrity. Among the three cytoskeletal components, intermediate filaments (the cytokeratin in epithelial cells) are the best candidates for this mechanical role. A model of the establishment of the cytokeratin network of an epithelial cell is proposed to study the dependence of its structural organization on extracellular mechanical environment. To implicitly describe the latter and its effects on the intracellular domain, we use mechanically regulated protein synthesis. Our model is a hybrid of a partial differential equation of parabolic type, governing the evolution of the concentration of cytokeratin, and a set of stochastic differential equations describing the dynamics of filaments. Each filament is described by a stochastic differential equation that reflects both the local interactions with the environment and the non-local interactions via the past history of the filament. A three-dimensional simulation model is derived from this mathematical model. This simulation model is then used to obtain examples of cytokeratin network architectures under given mechanical conditions, and to study the influence of several parameters.

Research paper thumbnail of Dynamics of in vitro intermediate filament length distributions

Journal of Theoretical Biology, 2013

An aggregation model with explicit expression of association rate constants is considered to stud... more An aggregation model with explicit expression of association rate constants is considered to study in vitro type III intermediate filament length distribution dynamics. Different assumptions on the properties of filaments and probability of aggregation are considered, leading to four models. Fitting of model responses to experimental data leads to the identification of the most appropriate model to represent each time point of the assembly. A combination of models allows the construction of a mixed model that represents well the complete assembly dynamics: it is found that the rate constants decrease with respect to filament size when the aggregation involves at least one short filament, whereas for longer filaments they are almost independent of size. The flexible nature of filaments is thus important in the assembly of intermediate filaments.

Research paper thumbnail of Gravitational Symmetry Breaking Leads to a Polar Liquid Crystal Phase of Microtubules In Vitro

Journal of Biological Physics, 2005

Recent space-flight experiments performed by Tabony's team provided further evidence that a micro... more Recent space-flight experiments performed by Tabony's team provided further evidence that a microgravity environment strongly affects the spatio-temporal organization of microtubule assemblies. Characteristic time and length scales were found that govern the organization of oriented bundles under Earth's gravitational field (GF). No such organization has been observed in a microgravity environment. This paper discusses physical mechanisms resulting in pattern formation under gravity and its disappearance in microgravity. The subtle interplay between chemical kinetics, diffusion, gravitational drift, thermal fluctuations, electrostatic interactions and liquid crystalline characteristics provides a plausible scenario.

Research paper thumbnail of A mathematical model for the keratin cycle of assembly and disassembly

IMA Journal of Applied Mathematics, 2013

We formulate a mathematical model to study the in vivo keratin organization in terms of repartiti... more We formulate a mathematical model to study the in vivo keratin organization in terms of repartition of the keratin material between three different structural states: soluble proteins, filament precursors and filamentous state. The model describes a cycle of assembly and disassembly of keratin material. A generic nucleation function and structural stability of filament precursors are assumed. It is established that the three structural states always coexist and that the repartition of keratin material never exhibits any cyclic behaviour. Under some conditions, it is shown that the choice of the nucleation function does not affect the qualitative behaviour of the system. However, it might change the stable repartition of the keratin material in the cell.