Cell Repolarization: A Bifurcation Study of Spatio-Temporal Perturbations of Polar Cells

Buttenschön, Andreas; Edelstein‐Keshet, Leah

doi:10.1007/s11538-022-01053-z

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…However, different modes of feedback between footprint and the Rho GT-Pase might make quantitative changes in the threshold where cells respond to the end of the footprint. Quantitative changes in sensitivity to repolarization have been found for a related question – how cells respond to optogenetic stimulation affecting different parts of the Rho GTPase system [47].…”

Section: Discussionmentioning

confidence: 99%

“…However, different feedback modes between footprint and the Rho GTPase might make quantitative changes in the threshold where cells respond to the end of the footprint. Quantitative changes in sensitivity to repolarization have been found for a related question -how cells respond to optogenetic stimulation affecting different parts of the Rho GTPase system (47). We have also neglected a possible feedback where changes in cell polarity alters deposition (34), instead keeping the deposition rate constant for simplicity.…”

Section: R a F Tmentioning

confidence: 99%

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Deposited footprints let cells switch between confined, oscillatory, and exploratory migration

Ipiña,

d’Alessandro,

Ladoux

et al. 2023

Preprint

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For eukaryotic cells to heal wounds, respond to immune signals, or metastasize, they must migrate, often by adhering to extracellular matrix. Cells may also secrete matrix factors, leaving behind a footprint that influences their crawling. Recent experiments showed that epithelial cells on micropatterned adhesive stripes move persistently in regions they have previously crawled over, where footprints have been formed, but barely advance into unexplored regions, creating an oscillatory migration of increasing amplitude. Here, we explore through mathematical modeling how footprint secretion and cell responses to footprint combine to allow cells to develop oscillation and other complex migratory motions. We simulate cell crawling with a phase field model coupled to a biochemical model of cell polarity, assuming local contact with the secreted footprint activates Rac1, a polarity protein at the front of the cell. Depending on the footprint secretion rate and the response to the footprint, cells on micropatterned lines can display a variety of types of motility, including confined, oscillatory, and persistent motion. On 2D substrates, we predict a transition between cells undergoing circular motion and cells developing a more exploratory phenotype. Our model shows how minor changes in a cell's interaction with its footprint can completely alter exploration, allowing cells to tightly regulate their motion, as well as leading to a wide spectrum of behaviors when secretion or sensing is variable from cell to cell. Consistent with our computational predictions, we find in earlier experimental data evidence of cells undergoing both circular and exploratory motion. Our work proposes a new paradigm for how cells regulate their own motility.

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Section: Discussionmentioning

confidence: 99%

Section: R a F Tmentioning

confidence: 99%

Deposited footprints let cells switch between confined, oscillatory, and exploratory migration

Ipiña,

d’Alessandro,

Ladoux

et al. 2023

Preprint

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show abstract

“…In some cases, this stimulus will repolarize a cell, whose initial Rho activity was concentrated in the rear. This reversal of polarity was quantified in two models using PDE bifurcation analysis ( Buttenschön and Edelstein-Keshet, 2022 ), mapping out how the signal intensity, coupled to the inherent cell parameters, elicits a response ( Figure 6A ). In some regimes, the cell does not repolarize (i), in others it loses polarization entirely (iii), while in a wedge-shaped region (ii), it repolarizes in a direction opposite to its initial polarity.…”

Section: What Type Of Theory Do We Need?mentioning

confidence: 99%

“…Insets: Kymographs showing spatiotemporal nucleation promoting factor (NPF) activity (yellow=high, blue=low) with time on horizontal and space on vertical axes. ( A ) is modified from Figure 6 in Buttenschön and Edelstein-Keshet, 2022 and ( B ) modified from Figure 8 in Liu et al, 2021 .…”

Section: What Type Of Theory Do We Need?mentioning

confidence: 99%

From actin waves to mechanism and back: How theory aids biological understanding

Beta

Edelstein‐Keshet

Gov

et al. 2023

eLife

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Actin dynamics in cell motility, division, and phagocytosis is regulated by complex factors with multiple feedback loops, often leading to emergent dynamic patterns in the form of propagating waves of actin polymerization activity that are poorly understood. Many in the actin wave community have attempted to discern the underlying mechanisms using experiments and/or mathematical models and theory. Here, we survey methods and hypotheses for actin waves based on signaling networks, mechano-chemical effects, and transport characteristics, with examples drawn from Dictyostelium discoideum, human neutrophils, Caenorhabditis elegans, and Xenopus laevis oocytes. While experimentalists focus on the details of molecular components, theorists pose a central question of universality: Are there generic, model-independent, underlying principles, or just boundless cell-specific details? We argue that mathematical methods are equally important for understanding the emergence, evolution, and persistence of actin waves and conclude with a few challenges for future studies.

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“…The Wave-pinning model on the other hand is based on a higher-order nonlinear positive feedback [15][16][17][18], and in contrast to the Turing-like models, can account for cell re-polarization (polarity reversal) upon change of signal localization. The robustness of the re-polarization is however conditioned on the signal strength and width [19]. However, it has not been studied whether the Wave-pinning model allows to integrate signals that do not change in space but are disrupted over time, as expected during a cell migration in complex tissue environment.…”

Section: Introductionmentioning

confidence: 99%

Non-asymptotic transients away from steady states determine cellular responsiveness to dynamic spatial-temporal signals

Nandan,

Koseska

2023

PLoS Comput Biol

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Majority of the theory on cell polarization and the understanding of cellular sensing and responsiveness to localized chemical cues has been based on the idea that non-polarized and polarized cell states can be represented by stable asymptotic switching between them. The existing model classes that describe the dynamics of signaling networks underlying polarization are formulated within the framework of autonomous systems. However these models do not simultaneously capture both, robust maintenance of polarized state longer than the signal duration, and retained responsiveness to signals with complex spatial-temporal distribution. Based on recent experimental evidence for criticality organization of biochemical networks, we challenge the current concepts and demonstrate that non-asymptotic signaling dynamics arising at criticality uniquely ensures optimal responsiveness to changing chemoattractant fields. We provide a framework to characterize non-asymptotic dynamics of system’s state trajectories through a non-autonomous treatment of the system, further emphasizing the importance of (long) transient dynamics, as well as the necessity to change the mathematical formalism when describing biological systems that operate in changing environments.

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Cell Repolarization: A Bifurcation Study of Spatio-Temporal Perturbations of Polar Cells

Cited by 9 publications

References 53 publications

Deposited footprints let cells switch between confined, oscillatory, and exploratory migration

Deposited footprints let cells switch between confined, oscillatory, and exploratory migration

From actin waves to mechanism and back: How theory aids biological understanding

Non-asymptotic transients away from steady states determine cellular responsiveness to dynamic spatial-temporal signals

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