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Article ; Online: The mechanism of MinD stability modulation by MinE in Min protein dynamics.

Carlquist, William C / Cytrynbaum, Eric N

2023 Volume 19, Issue 11, Page(s) e1011615

Abstract: The patterns formed both in vivo and in vitro by the Min protein system have attracted much interest because of the complexity of their dynamic interactions given the apparent simplicity of the component parts. Despite both the experimental and ... ...

Abstract	The patterns formed both in vivo and in vitro by the Min protein system have attracted much interest because of the complexity of their dynamic interactions given the apparent simplicity of the component parts. Despite both the experimental and theoretical attention paid to this system, the details of the biochemical interactions of MinD and MinE, the proteins responsible for the patterning, are still unclear. For example, no model consistent with the known biochemistry has yet accounted for the observed dual role of MinE in the membrane stability of MinD. Until now, a statistical comparison of models to the time course of Min protein concentrations on the membrane has not been carried out. Such an approach is a powerful way to test existing and novel models that are difficult to test using a purely experimental approach. Here, we extract time series from previously published fluorescence microscopy time lapse images of in vitro experiments and fit two previously described and one novel mathematical model to the data. We find that the novel model, which we call the Asymmetric Activation with Bridged Stability Model, fits the time-course data best. It is also consistent with known biochemistry and explains the dual MinE role via MinE-dependent membrane stability that transitions under the influence of rising MinE to membrane instability with positive feedback. Our results reveal a more complex network of interactions between MinD and MinE underlying Min-system dynamics than previously considered.
MeSH term(s)	Escherichia coli Proteins/metabolism ; Escherichia coli/metabolism ; Cell Cycle Proteins/metabolism ; Membrane Proteins/metabolism ; Models, Theoretical ; Adenosine Triphosphatases/metabolism
Chemical Substances	Escherichia coli Proteins ; Cell Cycle Proteins ; Membrane Proteins ; MinD protein, E coli (EC 3.6.1.-) ; Adenosine Triphosphatases (EC 3.6.1.-) ; MinE protein, E coli
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1011615
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Article ; Online: A Stochastic Model of Cortical Microtubule Anchoring and Mechanics Provides Regulatory Control of Microtubule Shape.

Tian, Tim Y Y / Macdonald, Colin B / Cytrynbaum, Eric N

Bulletin of mathematical biology

2023 Volume 85, Issue 11, Page(s) 103

Abstract: The organization of cortical microtubule arrays play an important role in the development of plant cells. Until recently, the direct mechanical influence of cell geometry on the constrained microtubule (MT) trajectories have been largely ignored in ... ...

Abstract	The organization of cortical microtubule arrays play an important role in the development of plant cells. Until recently, the direct mechanical influence of cell geometry on the constrained microtubule (MT) trajectories have been largely ignored in computational models. Modelling MTs as thin elastic rods constrained on a surface, a previous study examined the deflection of MTs using a fixed number of segments and uniform segment lengths between MT anchors. It is known that the resulting MT curves converge to geodesics as the anchor spacing approaches zero. In the case of long MTs on a cylinder, buckling has been found for transverse trajectories. There is a clear interplay between two factors in the problem of deflection: curvature of the membrane and the lengths of MT segments. Here, we examine the latter in detail, in the backdrop of a circular cylinder. In reality, the number of segments are not predetermined and their lengths are not uniform. We present a minimal, realistic model treating the anchor spacing as a stochastic process and examine the net effect on deflection. We find that, by tuning the ratio of growth speed to anchoring rate, it is possible to mitigate MT deflection and even prevent buckling for lengths significantly larger than the previously-derived critical buckling length. We suggest that this mediation of deflection by anchoring might provide cells with a means of preventing arrays from deflecting away from the transverse orientation.
MeSH term(s)	Mathematical Concepts ; Models, Biological ; Microtubules
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184905-0
ISSN	1522-9602 ; 0007-4985 ; 0092-8240
ISSN (online)	1522-9602
ISSN	0007-4985 ; 0092-8240
DOI	10.1007/s11538-023-01211-x
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Article ; Online: A multiscale computational model of YAP signaling in epithelial fingering behavior.

Mukhtar, Naba / Cytrynbaum, Eric N / Edelstein-Keshet, Leah

Biophysical journal

2022 Volume 121, Issue 10, Page(s) 1940–1948

Abstract: In epithelial-mesenchymal transition (EMT), cells organized into sheets break away and become motile mesenchymal cells. EMT plays a crucial role in wound healing, embryonic development, and cancer metastasis. Intracellular signaling in response to ... ...

Abstract	In epithelial-mesenchymal transition (EMT), cells organized into sheets break away and become motile mesenchymal cells. EMT plays a crucial role in wound healing, embryonic development, and cancer metastasis. Intracellular signaling in response to mechanical, topographic, or chemical stimuli can promote EMT. We present a multiscale model for EMT downstream of the protein YAP, which suppresses the cell-cell adhesion protein E-cadherin and activates the GTPase Rac1 that enhances cell migration. We first propose an ordinary differential equation (ODE) model for intracellular YAP/Rac1/E-cadherin interactions. The ODE model dynamics are bistable, accounting for both motile loose cells and adherent slower cells. We incorporate this model into a cellular Potts model simulation of two-dimensional wound healing using the open-source platform Morpheus. We show that, under suitable stimuli representing topographic cues, the sheet exhibits finger-like projections and EMT. Morphological differences and quantitative differences in YAP levels as well as variations in cell speed across the sheet are consistent with previous experimental observations of epithelial sheets grown on topographic features in vitro. The simulation is also consistent with experiments that knock down or overexpress YAP, inhibit Rac1, or block E-cadherin.
MeSH term(s)	Cadherins/metabolism ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Signal Transduction
Chemical Substances	Cadherins
Language	English
Publishing date	2022-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2022.04.010
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Article ; Online: Effects of age-targeted sequestration for COVID-19.

Jamieson-Lane, Alastair / Cytrynbaum, Eric

Journal of biological dynamics

2020 Volume 14, Issue 1, Page(s) 621–632

Abstract: We model the extent to which age-targeted protective sequestration can be used to reduce ICU admissions caused by novel coronavirus COVID-19. Using demographic data from New Zealand, we demonstrate that lowering the age threshold to 50 years of age ... ...

Abstract	We model the extent to which age-targeted protective sequestration can be used to reduce ICU admissions caused by novel coronavirus COVID-19. Using demographic data from New Zealand, we demonstrate that lowering the age threshold to 50 years of age reduces ICU admissions drastically and show that for sufficiently strict isolation protocols, sequestering one-third of the countries population for a total of 8 months is sufficient to avoid overwhelming ICU capacity throughout the entire course of the epidemic. Similar results are expected to hold for other countries, though some minor adaption will be required based on local age demographics and hospital facilities.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Betacoronavirus ; COVID-19 ; Child ; Child, Preschool ; Communicable Disease Control/methods ; Computer Simulation ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/transmission ; Critical Care ; Female ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Intensive Care Units/supply & distribution ; Male ; Middle Aged ; Models, Biological ; New Zealand/epidemiology ; Pandemics/prevention & control ; Patient Isolation/methods ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/transmission ; Quarantine/methods ; Risk Factors ; SARS-CoV-2 ; Young Adult
Keywords	covid19
Language	English
Publishing date	2020-07-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1751-3766
ISSN (online)	1751-3766
DOI	10.1080/17513758.2020.1795285
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Article ; Online: Effects of age-targeted sequestration for COVID-19

Jamieson-Lane, Alastair / Cytrynbaum, Eric

Journal of Biological Dynamics

2020 Volume 14, Issue 1, Page(s) 621–632

Keywords	Ecology ; Ecology, Evolution, Behavior and Systematics ; covid19
Language	English
Publisher	Informa UK Limited
Publishing country	uk
Document type	Article ; Online
ISSN	1751-3758
DOI	10.1080/17513758.2020.1795285
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Effects of age-targeted sequestration for COVID-19

Jamieson-Lane, Alastair / Cytrynbaum, Eric

J Biol Dyn

Abstract	We model the extent to which age-targeted protective sequestration can be used to reduce ICU admissions caused by novel coronavirus COVID-19. Using demographic data from New Zealand, we demonstrate that lowering the age threshold to 50 years of age reduces ICU admissions drastically and show that for sufficiently strict isolation protocols, sequestering one-third of the countries population for a total of 8 months is sufficient to avoid overwhelming ICU capacity throughout the entire course of the epidemic. Similar results are expected to hold for other countries, though some minor adaption will be required based on local age demographics and hospital facilities.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #680239
Database	COVID19

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Article ; Online: A Mathematical Model for the Kinetics of the MalFGK[Formula: see text] Maltose Transporter.

Hiller, Rebecca M / von Kügelgen, Julius / Bao, Huan / Van Hoa, Franck Duong / Cytrynbaum, Eric N

Bulletin of mathematical biology

2020 Volume 82, Issue 5, Page(s) 62

Abstract: The MalFGK[Formula: see text] transporter regulates the movement of maltose across the inner membrane of E. coli and serves as a model system for bacterial ATP binding cassette (ABC) importers. Despite the wealth of biochemical and structural data ... ...

Abstract	The MalFGK[Formula: see text] transporter regulates the movement of maltose across the inner membrane of E. coli and serves as a model system for bacterial ATP binding cassette (ABC) importers. Despite the wealth of biochemical and structural data available, a general model describing the various translocation pathways is still lacking. In this study, we formulate a mathematical model with the goal of determining the transporter reaction pathway, specifically looking at the order of binding events and conformation changes by which transport proceeds. Fitting our mathematical model to equilibrium binding data, we estimate the unknown equilibrium parameters of the system, several of which are key determinants of the transport process. Using these estimates along with steady-state ATPase rate data, we determine which of several possible reaction pathways is dominant, as a function of five underdetermined kinetic parameter values. Because neither experimental measurements nor estimates of certain kinetic rate constants are available, the problem of deciding which of the reaction pathways is responsible for transport remains unsolved. However, using the mathematical framework developed here, a firmer conclusion regarding the dominant reaction pathway as a function of MalE and maltose concentration could be drawn once these unknown kinetic parameters are determined.
MeSH term(s)	ATP-Binding Cassette Transporters/chemistry ; ATP-Binding Cassette Transporters/metabolism ; Biological Transport, Active ; Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/metabolism ; Kinetics ; Ligands ; Maltose/metabolism ; Mathematical Concepts ; Metabolic Networks and Pathways ; Models, Biological ; Protein Conformation
Chemical Substances	ATP-Binding Cassette Transporters ; Escherichia coli Proteins ; Ligands ; maltose transport system, E coli ; Maltose (69-79-4)
Language	English
Publishing date	2020-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184905-0
ISSN	1522-9602 ; 0007-4985 ; 0092-8240
ISSN (online)	1522-9602
ISSN	0007-4985 ; 0092-8240
DOI	10.1007/s11538-020-00737-8
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Article ; Online: Correction to: A Mathematical Model for the Kinetics of the MalFGK

Hiller, Rebecca M / von Kügelgen, Julius / Bao, Huan / Duong Van Hoa, Franck / Cytrynbaum, Eric N

Bulletin of mathematical biology

2020 Volume 82, Issue 7, Page(s) 92

Abstract: The original version of this article unfortunately contained a mistake. The co-author Dr. Franck Duong Van Hoa first name and last name were misinterpreted in the original publication. ...

Abstract	The original version of this article unfortunately contained a mistake. The co-author Dr. Franck Duong Van Hoa first name and last name were misinterpreted in the original publication.
Language	English
Publishing date	2020-07-11
Publishing country	United States
Document type	Published Erratum
ZDB-ID	184905-0
ISSN	1522-9602 ; 0007-4985 ; 0092-8240
ISSN (online)	1522-9602
ISSN	0007-4985 ; 0092-8240
DOI	10.1007/s11538-020-00772-5
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Book ; Online: Timing and Shape of Stochastic Autocatalytic Burst Formation

Jamieson-Lane, Alastair / Cytrynbaum, Eric N.

2019

Abstract: Chemical, physical and ecological systems passing through a saddle-node bifurcation will, momentarily, find themselves balanced at a semi-stable steady state. If perturbed by noise, such systems will escape from the zero-steady state, with escape time ... ...

Abstract	Chemical, physical and ecological systems passing through a saddle-node bifurcation will, momentarily, find themselves balanced at a semi-stable steady state. If perturbed by noise, such systems will escape from the zero-steady state, with escape time sensitive to noise. When the model is extended to include space, this leads to different points in space "escaping from zero" at different times, and uniform initial conditions nucleate into sharp peaks spread randomly across a nearly uniform background, a phenomena closely resembling nucleation during phase transition. We use Large Deviation Theory to determine burst shape and temporal scaling with respect to noise amplitude. These results give a prototype for a particular form of patternless symmetry breaking in the vicinity of a stability boundary, and demonstrates how microscopic noise can lead to macroscopic effects in such a region.
Keywords	Condensed Matter - Statistical Mechanics ; Mathematics - Probability ; 60G99
Subject code	612
Publishing date	2019-07-31
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: A buckling instability and its influence on microtubule orientation in plant cells

Bachmann, Sven / Froese, Richard / Cytrynbaum, Eric N

2019

Abstract: In growing plant cells, parallel ordering of microtubules (MTs) along the inner surface of the cell membrane influences the direction of cell expansion and thereby plant morphology. For correct expansion of organs that primarily grow by elongating, such ... ...

Abstract	In growing plant cells, parallel ordering of microtubules (MTs) along the inner surface of the cell membrane influences the direction of cell expansion and thereby plant morphology. For correct expansion of organs that primarily grow by elongating, such as roots and stems, MTs must bend in the high-curvature direction along the cylindrically shaped cell membrane in order to form the required circumferential arrays. Computational studies, which have recapitulated the self-organization of these arrays, ignored MT mechanics and assumed MTs follow geodesics of the cell surface. Here, we show, through analysis of a derived Euler-Lagrange equation, that an elastic MT constrained to a cylindrical surface will deflect away from geodesics and toward low curvature directions to minimize bending energy. This occurs when the curvature of the cell surface is relatively high for a given anchor density. In the limit of infinite anchor density, MTs always follow geodesics. We compare our analytical predictions to measured curvatures and anchor densities and find that the regime in which cells are forming these cortical arrays straddles the region of parameter space in which arrays must form under the antagonistic influence of this mechanically induced deflection. Although this introduces a potential obstacle to forming circumferentially orientated arrays that needs to be accounted for in the models, it also raises the question of whether plants use this mechanical phenomenon to regulate array orientation. The model also constitutes an elegant generalization of the classical Euler-bucking instability along with an intrinsic unfolding of the associated pitchfork bifurcation. Comment: To appear in SIAM Journal on Applied Mathematics (SIAP); v1->v2: change of title and reorganization of the presentation of the results
Keywords	Physics - Biological Physics ; Quantitative Biology - Subcellular Processes
Subject code	612
Publishing date	2019-04-08
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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