scholarly journals “Stick-slip dynamics of cell adhesion triggers spontaneous symmetry breaking and directional migration”

2018 ◽  
Author(s):  
K. Hennig ◽  
I. Wang ◽  
P. Moreau ◽  
L. Valon ◽  
S. DeBeco ◽  
...  
Keyword(s):  
Symmetry Breaking ◽  
Cell Motility ◽  
Spontaneous Symmetry Breaking ◽  
Single Cells ◽  
Traction Force ◽  
Stick Slip ◽  
Migration Assay ◽  
Cell Substrate ◽  
Adhesive Contacts

AbstractDirectional cell motility during organism and tissue development, homeostasis and disease requires symmetry breaking. This process relies on the ability of single cells to establish a front-rear polarity, and can occur in absence of external cues. The initiation of migration has been attributed to the spontaneous polarization of cytoskeleton components, while the spatiotemporal evolution of cytoskeletal forces arising from continuous mechanical cell-substrate interaction has yet to be resolved. Here, we establish a one-dimensional microfabricated migration assay that mimics complex in vivo fibrillar environment while being compatible with high-resolution force measurements, quantitative microscopy, and optogenetics. Quantification of morphometric and mechanical parameters reveals a generic stick-slip behavior initiated by contractility-dependent stochastic detachment of adhesive contacts at one side of the cell, which is sufficient to drive directional cell motility in absence of pre-established cytoskeleton polarity or morphogen gradients. A theoretical model validates the crucial role of adhesion dynamics during spontaneous symmetry breaking, proposing that the examined phenomenon can emerge independently of a complex self-polarizing system.One sentence summaryCells can autonomously break their symmetry through traction force oscillations (mechanical instabilities) that lead to stochastic detachment of adhesion patches on one side of the cell and the subsequent initiation of migration.

scholarly journals Stick-slip dynamics of cell adhesion triggers spontaneous symmetry breaking and directional migration of mesenchymal cells on one-dimensional lines

2020 ◽  
Vol 6 (1) ◽  
pp. eaau5670 ◽  
Author(s):  
K. Hennig ◽  
I. Wang ◽  
P. Moreau ◽  
L. Valon ◽  
S. DeBeco ◽  
...  
Keyword(s):  
Cell Motility ◽  
Single Cells ◽  
Stick Slip ◽  
One Dimensional ◽  
Migration Assay ◽  
3T3 Fibroblasts ◽  
Cell Substrate ◽  
Nih 3T3 ◽  
Adhesive Contacts

Directional cell motility relies on the ability of single cells to establish a front-rear polarity and can occur in the absence of external cues. The initiation of migration has often been attributed to the spontaneous polarization of cytoskeleton components, while the spatiotemporal evolution of cell-substrate interaction forces has yet to be resolved. Here, we establish a one-dimensional microfabricated migration assay that mimics the complex in vivo fibrillar environment while being compatible with high-resolution force measurements, quantitative microscopy, and optogenetics. Quantification of morphometric and mechanical parameters of NIH-3T3 fibroblasts and RPE1 epithelial cells reveals a generic stick-slip behavior initiated by contractility-dependent stochastic detachment of adhesive contacts at one side of the cell, which is sufficient to trigger cell motility in 1D in the absence of pre-established polarity. A theoretical model validates the crucial role of adhesion dynamics, proposing that front-rear polarity can emerge independently of a complex self-polarizing system.

scholarly journals Leishmania major Promastigotes Inhibit Dendritic Cell Motility In Vitro

2002 ◽  
Vol 70 (2) ◽  
pp. 1023-1026 ◽  
Author(s):  
Heather Jebbari ◽  
Andrew J. Stagg ◽  
Robert N. Davidson ◽  
Stella C. Knight
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cell Motility ◽  
Leishmania Major ◽  
Protective Role ◽  
Transwell Migration Assay ◽  
Migration Assay ◽  
Dose Dependent

ABSTRACT Using an in vitro transwell migration assay, we have demonstrated that products secreted by Leishmania major promastigotes inhibit the motility of dendritic cells (DC) by up to 93%. Inhibition was dose dependent and reversible. By inhibiting DC migration in vivo, L. major may therefore subvert DC from their potentially protective role during leishmaniasis.

scholarly journals Balance between cell−substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes

2015 ◽  
Vol 112 (16) ◽  
pp. 5045-5050 ◽  
Author(s):  
Erin Barnhart ◽  
Kun-Chun Lee ◽  
Greg M. Allen ◽  
Julie A. Theriot ◽  
Alex Mogilner
Keyword(s):  
Symmetry Breaking ◽  
Spontaneous Symmetry Breaking ◽  
Adhesion Strength ◽  
Network Flow ◽  
Critical Threshold ◽  
Stable States ◽  
Flow Rates ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion

Cells are dynamic systems capable of spontaneously switching among stable states. One striking example of this is spontaneous symmetry breaking and motility initiation in fish epithelial keratocytes. Although the biochemical and mechanical mechanisms that control steady-state migration in these cells have been well characterized, the mechanisms underlying symmetry breaking are less well understood. In this work, we have combined experimental manipulations of cell−substrate adhesion strength and myosin activity, traction force measurements, and mathematical modeling to develop a comprehensive mechanical model for symmetry breaking and motility initiation in fish epithelial keratocytes. Our results suggest that stochastic fluctuations in adhesion strength and myosin localization drive actin network flow rates in the prospective cell rear above a critical threshold. Above this threshold, high actin flow rates induce a nonlinear switch in adhesion strength, locally switching adhesions from gripping to slipping and further accelerating actin flow in the prospective cell rear, resulting in rear retraction and motility initiation. We further show, both experimentally and with model simulations, that the global levels of adhesion strength and myosin activity control the stability of the stationary state: The frequency of symmetry breaking decreases with increasing adhesion strength and increases with increasing myosin contraction. Thus, the relative strengths of two opposing mechanical forces—contractility and cell−substrate adhesion—determine the likelihood of spontaneous symmetry breaking and motility initiation.

scholarly journals Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration

2021 ◽  
Vol 22 (8) ◽  
pp. 3871
Author(s):  
Vittorio Abruzzese ◽  
Ilenia Matera ◽  
Fabio Martinelli ◽  
Monica Carmosino ◽  
Prashant Koshal ◽  
...  
Keyword(s):  
Cell Motility ◽  
Purinergic Signaling ◽  
Antioxidant Properties ◽  
Pseudoxanthoma Elasticum ◽  
Ectopic Calcification ◽  
Inherited Disease ◽  
Migration Assay ◽  
Gene And Protein Expression

Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5′-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids.

scholarly journals Collective cell migration: leadership, invasion and segregation

2012 ◽  
Vol 9 (77) ◽  
pp. 3268-3278 ◽  
Author(s):  
Alexandre J. Kabla
Keyword(s):  
Cell Motility ◽  
Cancer Metastasis ◽  
Single Cells ◽  
Collective Effects ◽  
Collective Cell Migration ◽  
Broad Array ◽  
Coordination Process ◽  
Sheet Migration

A number of biological processes, such as embryo development, cancer metastasis or wound healing, rely on cells moving in concert. The mechanisms leading to the emergence of coordinated motion remain however largely unexplored. Although biomolecular signalling is known to be involved in most occurrences of collective migration, the role of physical and mechanical interactions has only been recently investigated. In this study, a versatile framework for cell motility is implemented in silico in order to study the minimal requirements for the coordination of a group of epithelial cells. We find that cell motility and cell–cell mechanical interactions are sufficient to generate a broad array of behaviours commonly observed in vitro and in vivo . Cell streaming, sheet migration and susceptibility to leader cells are examples of behaviours spontaneously emerging from these simple assumptions, which might explain why collective effects are so ubiquitous in nature. The size of the population and its confinement appear, in particular, to play an important role in the coordination process. In all cases, the complex response of the population can be predicted from the knowledge of the correlation length of the velocity field measured in the bulk of the epithelial layer. This analysis provides also new insights into cancer metastasis and cell sorting, suggesting, in particular, that collective invasion might result from an emerging coordination in a system where single cells are mechanically unable to invade.

scholarly journals Stick-Slip Dynamics of Migrating Cells on Viscoelastic Substrates

2019 ◽  
Author(s):  
Partho Sakha De ◽  
Rumi De
Keyword(s):  
Focal Adhesions ◽  
Traction Force ◽  
Reaction Diffusion ◽  
Substrate Stiffness ◽  
Retrograde Flow ◽  
Stick Slip ◽  
Cell Substrate ◽  
Elastic Substrates ◽  
Individual Bond ◽  
Stick Slip Motion

Stick-slip motion, a common phenomenon observed during crawling of cells, is found to be strongly sensitive to the substrate stiffness. Stick-slip behaviours have previously been investigated typically using purely elastic substrates. For a more realistic understanding of this phenomenon, we propose a theoretical model to study the dynamics on a viscoelastic substrate. Our model based on a reaction-diffusion framework, incorporates known important interactions such as retrograde flow of actin, myosin contractility, force dependent assembly and disassembly of focal adhesions coupled with cell-substrate interaction. We show that consideration of a viscoelastic substrate not only captures the usually observed stick-slip jumps, but also predicts the existence of an optimal substrate viscosity corresponding to maximum traction force and minimum retrograde flow which was hitherto unexplored. Moreover, our theory predicts the time evolution of individual bond force that characterizes the stick-slip patterns on soft versus stiff substrates. Our analysis also elucidates how the duration of the stick-slip cycles are affected by various cellular parameters.

scholarly journals Stick-Slip model for actin-driven cell protrusions, cell polarisation and crawling

2020 ◽  
Author(s):  
Pierre Sens
Keyword(s):  
Symmetry Breaking ◽  
Spontaneous Symmetry Breaking ◽  
Biochemical Network ◽  
Cellular Mechanics ◽  
Stick Slip ◽  
Substrate Adhesion ◽  
Propagating Waves ◽  
Intracellular Forces ◽  
Cell Motion ◽  
Cytoskeleton Dynamics

Cell crawling requires the generation of intracellular forces by the cytoskeleton and their transmission to an extracellular substrate through specific adhesion molecules. Crawling cells show many features of excitable systems, such as spontaneous symmetry breaking and crawling in the absence of external cues, and periodic and propagating waves of activity. Mechanical instabilities in the active cytoskeleton network and feedback loops in the biochemical network of activators and repressors of cytoskeleton dynamics have been invoked to explain these dynamical features. Here, we show that the interplay between the dynamics of cell-substrate adhesion and linear cellular mechanics is sufficient to reproduce many non-linear dynamical patterns observed in spreading and crawling cells. Using an analytical formalism of the molecular clutch model of cell adhesion, regulated by local mechanical forces, we show that cellular traction forces exhibit a stick-slip dynamics resulting in periodic waves of protrusion/retraction and propagating waves along the cell edge. This can explain spontaneous symmetry breaking and polarisation of spreading cells, leading to steady crawling or bipedal motion, and bistability, where persistent cell motion requires a sufficiently strong transient external stimulus. The model also highlight the role of membrane tension in providing the long-range mechanical communication across the cell required for symmetry breaking.

scholarly journals Stick–slip model for actin-driven cell protrusions, cell polarization, and crawling

2020 ◽  
Vol 117 (40) ◽  
pp. 24670-24678 ◽  
Author(s):  
Pierre Sens
Keyword(s):  
Symmetry Breaking ◽  
Spontaneous Symmetry Breaking ◽  
Cell Polarization ◽  
Biochemical Network ◽  
Cellular Mechanics ◽  
Stick Slip ◽  
Nonlinear Dynamical ◽  
Substrate Adhesion ◽  
Propagating Waves ◽  
Intracellular Forces

Cell crawling requires the generation of intracellular forces by the cytoskeleton and their transmission to an extracellular substrate through specific adhesion molecules. Crawling cells show many features of excitable systems, such as spontaneous symmetry breaking and crawling in the absence of external cues, and periodic and propagating waves of activity. Mechanical instabilities in the active cytoskeleton network and feedback loops in the biochemical network of activators and repressors of cytoskeleton dynamics have been invoked to explain these dynamical features. Here, I show that the interplay between the dynamics of cell–substrate adhesion and linear cellular mechanics is sufficient to reproduce many nonlinear dynamical patterns observed in spreading and crawling cells. Using an analytical formalism of the molecular clutch model of cell adhesion, regulated by local mechanical forces, I show that cellular traction forces exhibit stick–slip dynamics resulting in periodic waves of protrusion/retraction and propagating waves along the cell edge. This can explain spontaneous symmetry breaking and polarization of spreading cells, leading to steady crawling or bipedal motion, and bistability, where persistent cell motion requires a sufficiently strong transient external stimulus. The model also highlights the role of membrane tension in providing the long-range mechanical communication across the cell required for symmetry breaking.

scholarly journals Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration

2021 ◽  
Vol 22 (7) ◽  
pp. 3437
Author(s):  
Vittorio Abruzzese ◽  
Ilenia Matera ◽  
Fabio Martinelli ◽  
Monica Carmosino ◽  
Prashant Koshal ◽  
...  
Keyword(s):  
Cell Motility ◽  
Purinergic Signaling ◽  
Antioxidant Properties ◽  
Pseudoxanthoma Elasticum ◽  
Ectopic Calcification ◽  
Inherited Disease ◽  
Migration Assay ◽  
Gene And Protein Expression

Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5′-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids.

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