Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo Agustín; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Berre, Maël Le; Lankar, Danielle; Piolot, Tristan; Adelstein, Robert S.; Zhang, Yingfan; Sixt, Michael; Jacobelli, Jordan; Bénichou, Olivier; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana-María

doi:10.1038/ncomms8526

Cited by 136 publications

(192 citation statements)

References 47 publications

(69 reference statements)

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“…Regarding the mechanical behavior of the cell, we notice that the maximum stress is reached when the surface force is applied, and, next, the cell attains a more relaxed state. Taking into account the experimental results obtained for interstitial migration in microfluidic devices in [2,29], the obtained results prove that the proposed model reproduce qualitatively the expected behavior of a cell in interstitial migration.…”

Section: Discussionsupporting

confidence: 67%

Modeling Confined Cell Migration Mediated by Cytoskeleton Dynamics

Sánchez

García-Aznar

2018

Computation

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Abstract:Cell migration is an important biological process that has generated increasing interest during the last several years. This process is based on three phases: protrusion at the front end of the cell, de-adhesion at the rear end and contraction of the cell body, all of them coordinated due to the polymerization/depolymerization of certain cytoskeletal proteins. The aim of this work is to present a mathematical model to simulate the actin polymerization/depolymerization process that regulates the final outcome of cell migration process, considering all the above phases, in a particular case: when the cell is confined in a microfluidic channel. Under these specific conditions, cell migration can be approximated by using one-dimensional simulations. We will propose a system of reaction-diffusion equations to simulate the behavior of the cytoskeletal proteins responsible for protrusion and contraction in the cell, coupled with the mechanical response of the cell, computing its deformations and stresses. Furthermore, a numerical procedure is presented in order to simulate the whole process in a moving and deformable domain corresponding to the cell body.

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Section: Discussionsupporting

confidence: 67%

Modeling Confined Cell Migration Mediated by Cytoskeleton Dynamics

Sánchez

García-Aznar

2018

Computation

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“…Major histocompatibility complex II (MHC-II)-dependent rearrangements of myosin II, which are required for efficient macropinocytosis at the cell anterior in dendritic cells, are incompatible with cell migration (Chabaud et al, 2015). This is similar to the situation in amoebae, where chemotaxis towards folic acid is impaired when high-frequency macropinocytosis occurs, again highlighting the broad similarities that could extend back to the common ancestors of Metazoa and amoebae (Veltman et al, 2014).…”

Section: Macropinocytosis In Immunity and Infectionmentioning

confidence: 72%

Uses and abuses of macropinocytosis

Bloomfield

Kay

2016

Journal of Cell Science

155

171

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Macropinocytosis is a means by which eukaryotic cells ingest extracellular liquid and dissolved molecules. It is widely conserved amongst cells that can take on amoeboid form and, therefore, appears to be an ancient feature that can be traced back to an early stage of evolution. Recent advances have highlighted how this endocytic process can be subverted during pathology -certain cancer cells use macropinocytosis to feed on extracellular protein, and many viruses and bacteria use it to enter host cells. Prion and prion-like proteins can also spread and propagate from cell to cell through macropinocytosis. Progress is being made towards using macropinocytosis therapeutically, either to deliver drugs to or cause cell death by inducing catastrophically rapid fluid uptake. Mechanistically, the Ras signalling pathway plays a prominent and conserved activating role in amoebae and in mammals; mutant amoebae with abnormally high Ras activity resemble tumour cells in their increased capacity for growth using nutrients ingested through macropinocytosis. This Commentary takes a functional and evolutionary perspective to highlight progress in understanding and use of macropinocytosis, which is an ancient feeding process used by single-celled phagotrophs that has now been put to varied uses by metazoan cells and is abused in disease states, including infection and cancer.

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“…Solid tumors are well known for their poor permeability to drugs, i.e., low porosity, and macrophage immobilization can in part be due to an inability to “eat and run,” with similar antagonism already known between endocytic and migratory pathways for Dyctiostilium amoeba [39] and dendritic cells [40]. Nuclear lamins set nuclear stiffness, and a cell with high lamin levels (Figure 5C) is impeded in 3D migration [41, 42] with similar effects expected after engulfment of another cell (Figures 1B and 1C).…”

Section: Discussionmentioning

confidence: 99%

SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors

et al. 2017

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SUMMARY Marrow-derived macrophages are highly phagocytic, but whether they can also traffic into solid tumors and engulf cancer cells is questionable, given the well-known limitations of tumor-associated macrophages (TAMs). Here, SIRPα on macrophages from mouse and human marrow was inhibited to block recognition of its ligand, the “marker of self” CD47 on all other cells. These macrophages were then systemically injected into mice with fluorescent human tumors that had been antibody targeted. Within days, the tumors regressed, and single-cell fluorescence analyses showed that the more the macrophages engulfed, the more they accumulated within regressing tumors. Human-marrow-derived macrophages engorged on the human tumors, while TAMs were minimally phagocytic, even toward CD47-knockdown tumors. Past studies had opsonized tumors in situ with antibody and/or relied on mouse TAMs but had not injected SIRPα-inhibited cells; also, unlike past injections of anti-CD47, blood parameters remained normal and safe. Consistent with tumor-selective engorge-and-accumulate processes in vivo, phagocytosis in vitro inhibited macrophage migration through micropores that mimic features of dense 3D tissue. Accumulation of SIRPα-inhibited macrophages in tumors favored tumor regression for 1–2 weeks, but donor macrophages quickly differentiated toward non-phagocytic, high-SIRPα TAMs. Analyses of macrophages on soft (like marrow) or stiff (like solid tumors) collagenous gels demonstrated a stiffness-driven, retinoic-acid-modulated upregulation of SIRPα and the mechanosensitive nuclear marker lamin-A. Mechanosensitive differentiation was similarly evident in vivo and likely limited the anti-tumor effects, as confirmed by re-initiation of tumor regression by fresh injections of SIRPα-inhibited macrophages. Macrophage motility, phagocytosis, and differentiation in vivo are thus coupled.

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Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

Cited by 136 publications

References 47 publications

Modeling Confined Cell Migration Mediated by Cytoskeleton Dynamics

Modeling Confined Cell Migration Mediated by Cytoskeleton Dynamics

Uses and abuses of macropinocytosis

SIRPA-Inhibited, Marrow-Derived Macrophages Engorge, Accumulate, and Differentiate in Antibody-Targeted Regression of Solid Tumors

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