Macropinocytosis Overcomes Directional Bias in Dendritic Cells Due to Hydraulic Resistance and Facilitates Space Exploration

Moreau, Hélène D.; Blanch-Mercader, Carles; Attia, Rafaële; Maurin, Mathieu; Alraies, Zahraa; Sanséau, Doriane; Malbec, Odile; Delgado, Maria–Graciela; Bousso, Philippe; Joanny, Jean‐François; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana-María

doi:10.1016/j.devcel.2019.03.024

Cited by 80 publications

(70 citation statements)

References 62 publications

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“…To further investigate this aspect, we added a fluorescent dye FITC Dextran (70kD) into the loading channel at the right-hand side of the chip, together with the chemoattractant. We observed that as the cell protrudes into the blind channels the fluid was displaced around the leading edge, while there was no evidence for micropinocytosis as has been reported for immature dendritic cells recently (32). These results appear to indicate that that cells are only able to migrate into dead-end channels under conditions where they can deform sufficiently to shunt some fluid between the wall and membrane to generate space to move into.…”

Section: Decoupling Chemical Signal From Hydraulic Resistancesupporting

confidence: 66%

“…This is assumed to create a net influx of water at the leading edge and a net outflow at the uropod driving the cells motion and represents an alternative to the actin-driven motion ('Osmotic Engine Model' (39)). Recent work by Moreau et al (32) suggested that immature dendritic cells (DCs) cells could cope with high hydraulic resistance via a high level of macro-pinocytosis, that allows fluid transport across the cell and thereby exploration of dead-end channels (40). Mature DCs down-regulate macropinocytosis and lose the ability to penetrate dead-end channels.…”

Section: Discussionmentioning

confidence: 99%

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Chemotaxis overrides Barotaxis during Directional Decision-Making inDictyostelium discoideum

Belotti

McGloin

Weijer

2020

Preprint

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Neutrophils and dendritic cells have, besides their well characterised chemotactic movement responses, been shown to be able to detect and respond to local differences in hydraulic resistance (barotaxis). Furthermore, for neutrophils, it has been suggested that barotaxis overrides chemotaxis. Here, we investigate whether Dictyostelium cells also respond to hydraulic resistance or primarily to chemical gradients using an asymmetric bifurcating micro-channel. This channel design allows us to decouple hydraulic and chemical stimuli, by providing a choice between moving up a chemical gradient or down a chemical gradient into a channel with 100 times lower hydraulic resistance. Under these conditions chemotaxis always overrides barotaxis. Cells confronted by a microchannel bifurcation are observed to often partially split their leading edge and to start moving into both channels. Cells in steeper cAMP gradients, that move faster, split more readily. The decision to retract the pseudopod moving away from the cAMP source is made when the average velocity of the pseudopod moving up the cAMP gradient is 20% higher than the average velocity of the pseudopod moving down the gradient. Surprisingly, this decision threshold is independent of the steepness of the cAMP gradient and speed of movement. It indicates that a critical force imbalance threshold underlies the repolarisation decision. Significance StatementWe investigate the directional 'decision-making' of Dictyostelium discoideum cells migrating within engineered micro-channels harbouring asymmetric bifurcations. Unlike neutrophils and immature dendritic cells, Dictyostelium cells strongly prioritise chemical over barotactic guidance cues. Cells in steeper cAMP gradients migrate at higher speeds, split their leading edges more readily when confronted with a bifurcation in the channel. The decision to retract a pseudopod pointing in an unfavourable direction occurs when a critical tension gradient between two competing pseudopods is surpassed. These experiments show that although barotaxis is not a major guidance cue, cellular mechanics plays a major role in leading edge dynamics, including front splitting and polarisation and retraction.

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Section: Decoupling Chemical Signal From Hydraulic Resistancesupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Chemotaxis overrides Barotaxis during Directional Decision-Making inDictyostelium discoideum

Belotti

McGloin

Weijer

2020

Preprint

View full text Add to dashboard Cite

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“…On the other hand, the capacity of migration following hydraulic gradients in the absence of chemical cues is called barotaxis. Several experiments have demonstrated that cells confined to bifurcating channels select the channel of lower hydraulic resistance to orientate and migrate [36,37]. Interestingly, barotaxis does not need chemical attractors, although both barotaxis and chemotaxis may cooperate influencing cell migration, for example in neutrophils [36] and dendritic cells [37], under specific circumstances.…”

Section: External Stimuli Migration and Cancermentioning

confidence: 99%

“…Several experiments have demonstrated that cells confined to bifurcating channels select the channel of lower hydraulic resistance to orientate and migrate [36,37]. Interestingly, barotaxis does not need chemical attractors, although both barotaxis and chemotaxis may cooperate influencing cell migration, for example in neutrophils [36] and dendritic cells [37], under specific circumstances. In a system of competition between chemotaxis with the peptide fMLP against barotaxis, Prentice-Mott et al [36] showed that large cells with high asymmetrical capacities did not respond to chemotactic stimulus and directed their movements to low-resistance channels, whereas neutrophils (small cells with lesser asymmetric potential) could successfully overcome high hydraulic pressures to reach the chemotactic stimulus.…”

Section: External Stimuli Migration and Cancermentioning

confidence: 99%

Cell Motility and Cancer

Fuente

López

2020

Cancers

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Cell migration is an essential systemic behavior, tightly regulated, of all living cells endowed with directional motility that is involved in the major developmental stages of all complex organisms such as morphogenesis, embryogenesis, organogenesis, adult tissue remodeling, wound healing, immunological cell activities, angiogenesis, tissue repair, cell differentiation, tissue regeneration as well as in a myriad of pathological conditions. However, how cells efficiently regulate their locomotion movements is still unclear. Since migration is also a crucial issue in cancer development, the goal of this narrative is to show the connection between basic findings in cell locomotion of unicellular eukaryotic organisms and the regulatory mechanisms of cell migration necessary for tumor invasion and metastases. More specifically, the review focuses on three main issues, (i) the regulation of the locomotion system in unicellular eukaryotic organisms and human cells, (ii) how the nucleus does not significantly affect the migratory trajectories of cells in two-dimension (2D) surfaces and (iii) the conditioned behavior detected in single cells as a primitive form of learning and adaptation to different contexts during cell migration. New findings in the control of cell motility both in unicellular organisms and mammalian cells open up a new framework in the understanding of the complex processes involved in systemic cellular locomotion and adaptation of a wide spectrum of diseases with high impact in the society such as cancer.

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“…We therefore predict that speed-persistence coupling may not be visible in in vivo imaging data of T cells patrolling the epidermis: in such an environment, both speed and persistence likely reflect the maximum of what is feasible given the environmental constraints rather than being the result of an intrinsic coupling. In complex, highly restrictive environments, cells may choose the path of least resistance (39), with a lesser role for their intrinsic polarity mechanism in this context. But compared to most other tissues, the epidermis is an extreme example of a confining environment.…”

Section: Discussionmentioning

confidence: 99%

Actin-inspired feedback couples speed and persistence in a Cellular Potts Model of cell migration

Wortel

Niculescu

et al. 2018

Preprint

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8 9T cells are key effector cells in the immune system that are well-known for their ability to adapt their shape and 10 behavior to environmental cues. It has been suggested that these highly diverse, context-dependent migration 11 patterns reflect an optimization process -where T cells adjust motility parameters such as speed and persistence 12 to aid their search for antigen. Whereas models investigating such "search strategies" typically treat speed and 13 persistence as independent variables, one aspect of cell motility was recently found to be conserved across 14 a large variety of cell types: fast-moving cells turn less frequently. This raises the question whether T cells 15 can tune speed and persistence independently of each other. We therefore investigated to what extent this 16 universal coupling between cell speed and persistence (UCSP) shapes the behavior of migrating T cells. We 17 first show that the UCSP emerges spontaneously in an in silico Cellular Potts Model (CPM) of T cell migration. 18 Our model shows a link between the UCSP and cell shape dynamics, which put an upper bound on both the 19 speed and the persistence a cell can reach. We then use the CPM to examine how environmental constraints 20 affect motility patterns of T cells migrating in the crowded environments they also face in vivo, and show that T 21 cells completely lose their speed-persistence coupling when confined in a densely packed environment such 22 as the epidermis. Thus, although our model further highlights the validity of the UCSP in migrating cells, it 23 also demonstrates that environmental factors may overrule this coupling. Our data show that T cell motility 24 parameters are subject to both cell-intrinsic and extrinsic constraints, suggesting that "optimal" T cell search 25 strategies may not always be attainable in vivo. 26 1 28 T cells have the rare ability to migrate in nearly all tissues within the human body. Especially in tissues with a 29 high risk of infection -like the lung, the gut, and the skin -T cells are continuously on the move in search of 30 foreign invaders. Furthermore, migration in lymphoid organs such as the thymus and lymph nodes is crucial 31 for T cell function. 32Although T cells preserve their motility in these different contexts, they do adapt their morphology and 33 migratory behavior to environmental cues. It has been suggested that this remarkably flexible behavior reflects 34 different "search strategies" that allow T cells to maximize the chance of encountering antigen (Krummel et al., 35 2016). For example, naive T cells rapidly crawl along a network of stromal cells in the lymph node, alternating 36 between short intervals of persistent movement and random changes in direction (Miller et al., 2002(Miller et al., , 2003 37 Bajnoff et al., 2006; Beauchemin et al., 2007). This "stop and go" behavior allows them to cover large areas of the 38 lymph node in a short amount of time, and appears to be a good strategy for finding rare antigens without prior 39 information o...

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Macropinocytosis Overcomes Directional Bias in Dendritic Cells Due to Hydraulic Resistance and Facilitates Space Exploration

Cited by 80 publications

References 62 publications

Chemotaxis overrides Barotaxis during Directional Decision-Making inDictyostelium discoideum

Chemotaxis overrides Barotaxis during Directional Decision-Making inDictyostelium discoideum

Cell Motility and Cancer

Actin-inspired feedback couples speed and persistence in a Cellular Potts Model of cell migration

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