A Dynamic Model of Chemoattractant-Induced Cell Migration

Yang, Hao; Gou, Xue; Wang, Yong; Fahmy, Tarek M.; Leung, Anskar Y.H.; J, Lu; Sun, Dong

doi:10.1016/j.bpj.2014.12.060

Cited by 33 publications

(20 citation statements)

References 30 publications

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“…This term biases cells to polarize toward increasing c , but assumes the strength of this chemotaxis to c is independent of the gradient strength, once the gradient strength is above the threshold g 0 . The saturation of polarization is supported by recent experiments in T cells [ 31 ]. In other cell types other behaviors may be occur [ 32 ]; modifying this assumption would change the density and number of contacts in the cluster, leading to potential quantitative changes.…”

Section: Modelsupporting

confidence: 61%

Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

et al. 2016

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Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.

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Section: Modelsupporting

confidence: 61%

Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

et al. 2016

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“…In physiology, both TCR and pMHC are linked to actively motile cell membranes, where they are surrounded by adhesive molecules and coreceptors roughly of the same short dimensions (such as CD4 or CD8, CD2, CD28, and their respective ligands) or moderately larger (such as LFA-1 and its ligand ICAM-1), but also by much larger sterically repulsive molecules such as CD45, CD43, and CD148 (29,30). The interaction takes place in a context of mechanical forces: The T lymphocyte crawling on the APC surface while TCRs probe their ligands creates a mechanical shear force in the order of 1,000 pN at the cell scale (31). Motion in the axis perpendicular to membrane plane due to membrane fluctuations exists as in other cell types (32), but the T lymphocyte also probes the APC by extending and retracting microvilli that are enriched in TCRs (33).…”

Section: Discussion What Is the Physiological Relevance Of Single Tcrmentioning

confidence: 99%

TCR–pMHC kinetics under force in a cell-free system show no intrinsic catch bond, but a minimal encounter duration before binding

Limozin

Bridge

Bongrand

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The T cell receptor (TCR)–peptide-MHC (pMHC) interaction is the only antigen-specific interaction during T lymphocyte activation. Recent work suggests that formation of catch bonds is characteristic of activating TCR–pMHC interactions. However, whether this binding behavior is an intrinsic feature of the molecular bond, or a consequence of more complex multimolecular or cellular responses, remains unclear. We used a laminar flow chamber to measure, first, 2D TCR–pMHC dissociation kinetics of peptides of various activating potency in a cell-free system in the force range (6 to 15 pN) previously associated with catch–slip transitions and, second, 2D TCR–pMHC association kinetics, for which the method is well suited. We did not observe catch bonds in dissociation, and the off-rate measured in the 6- to 15-pN range correlated well with activation potency, suggesting that formation of catch bonds is not an intrinsic feature of the TCR–pMHC interaction. The association kinetics were better explained by a model with a minimal encounter duration rather than a standard on-rate constant, suggesting that membrane fluidity and dynamics may strongly influence bond formation.

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“…It has been postulated that ILPs can sense the stiffness of endothelial cells by “tiptoing” their surface ( 32 , 34 , 35 ). More recently, Yang et al ( 36 ) described the forces developed by chemotactic T lymphocytes. A laser trap was used to position two beads, one as source of chemokine gradient and the other to measure the forces exerted by the migrating T lymphocytes (in their case, the Jurkat leukemic T cell line).…”

Section: Forces In T Cellsmentioning

confidence: 99%

Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse

Hivroz

Saitakis

2016

Front. Immunol.

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T lymphocyte activation is a pivotal step of the adaptive immune response. It requires the recognition by T-cell receptors (TCR) of peptides presented in the context of major histocompatibility complex molecules (pMHC) present at the surface of antigen-presenting cells (APCs). T lymphocyte activation also involves engagement of costimulatory receptors and adhesion molecules recognizing ligands on the APC. Integration of these different signals requires the formation of a specialized dynamic structure: the immune synapse. While the biochemical and molecular aspects of this cell–cell communication have been extensively studied, its mechanical features have only recently been addressed. Yet, the immune synapse is also the place of exchange of mechanical signals. Receptors engaged on the T lymphocyte surface are submitted to many tensile and traction forces. These forces are generated by various phenomena: membrane undulation/protrusion/retraction, cell mobility or spreading, and dynamic remodeling of the actomyosin cytoskeleton inside the T lymphocyte. Moreover, the TCR can both induce force development, following triggering, and sense and convert forces into biochemical signals, as a bona fide mechanotransducer. Other costimulatory molecules, such as LFA-1, engaged during immune synapse formation, also display these features. Moreover, T lymphocytes themselves are mechanosensitive, since substrate stiffness can modulate their response. In this review, we will summarize recent studies from a biophysical perspective to explain how mechanical cues can affect T lymphocyte activation. We will particularly discuss how forces are generated during immune synapse formation; how these forces affect various aspects of T lymphocyte biology; and what are the key features of T lymphocyte response to stiffness.

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A Dynamic Model of Chemoattractant-Induced Cell Migration

Cited by 33 publications

References 30 publications

Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

TCR–pMHC kinetics under force in a cell-free system show no intrinsic catch bond, but a minimal encounter duration before binding

Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse

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