Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps

Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence–based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell–cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology.

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Emergence of single cell mechanical behavior and polarity within epithelial monolayers drives collective cell migration

10.1101/2019.12.16.875567 ◽

2019 ◽

Author(s):

Shreyansh Jain ◽

Victoire M.L. Cachoux ◽

Gautham H.N.S. Narayana ◽

Simon de Beco ◽

Joseph D’Alessandro ◽

...

Keyword(s):

Cell Migration ◽

Single Cell ◽

Large Scale ◽

Cancer Metastasis ◽

Cell Junctions ◽

Collective Cell Migration ◽

Convergent Extension ◽

Cell Dynamics

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis1,2. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions3,4. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring shaped patterns that recapitulate rotational movements observed in vitro in cellular monolayers and in vivo in genitalia or follicular cell rotation5–7. Using our system, we demonstrated that cells follow coordinated rotational movements after the establishment of directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front-back polarity within each single cell but does not require the maintenance of cell-cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple in vitro and in vivo situations5,6,8,9 can arise from single cell behavior through a sustained memory of cell polarity.

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Src42A required for collective border cell migration in vivo

10.1101/186049 ◽

2017 ◽

Cited By ~ 1

Author(s):

Yasmin Sallak ◽

Alba Yurani Torres ◽

Hongyan Yin ◽

Denise Montell

Keyword(s):

Cell Migration ◽

Cell Junctions ◽

Collective Cell Migration ◽

Border Cells ◽

Border Cell ◽

Border Cell Migration ◽

And Migration ◽

Drosophila Ovary ◽

E Cadherin

AbstractThe tyrosine kinase Src is over-expressed in numerous human cancers and is associated with poor prognosis. While Src has been extensively studied, its contributions to collective cell migration in vivo remain incompletely understood. Here we show that Src42A, but not Src64, is required for the specification and migration of the border cells in the Drosophila ovary, a well-developed and genetically tractable in vivo cell migration model. We found active Src42A enriched at border cell/nurse cell interfaces, where E-cadherin is less abundant, and depleted from border cell/border cell and border cell/polar cell junctions where E-cadherin is more stable, whereas total Src42A protein co-localizes with E-cadherin. Over-expression of wild type Src42A mislocalized Src activity and prevented border cell migration. Constitutively active or kinase dead forms of Src42A also impeded border cells. These findings establish border cells as a model for investigating the mechanisms of action of Src in cooperative, collective, cell-on-cell migration in vivo.

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Microtubule deacetylation reduces cell stiffness to allow the onset of collective cell migration in vivo

10.1101/2021.08.12.456059 ◽

2021 ◽

Author(s):

Cristian L Marchant ◽

Abdul N Malmi-Kakkada ◽

Jaime A Espina ◽

Elias H Barriga

Keyword(s):

Cell Migration ◽

Cancer Metastasis ◽

Mechanical Response ◽

Substrate Stiffness ◽

Cell Stiffness ◽

Collective Cell Migration ◽

Force Microscopy ◽

Atomic Force

Embryogenesis, tissue repair and cancer metastasis rely on collective cell migration (CCM). In vitro studies propose that migrating cells are stiffer when exposed to stiff substrates, known to allow CCM, but softer when plated in compliant non-permissive surfaces. Here, by combining in vivo atomic force microscopy (iAFM) and modelling we reveal that to collectively migrate in vivo, cells require to dynamically decrease their stiffness in response to the temporal stiffening of their native substrate. Moreover, molecular and mechanical perturbations of embryonic tissues uncover that this unexpected cell mechanical response is achieved by a new mechanosensitive pathway involving Piezo1-mediated microtubule deacetylation. Finally, lowering microtubule acetylation and consequently cell stiffness was sufficient to allow CCM in soft non-permissive substrates, suggesting that a fixed value of substrate stiffness is not as essential for CCM as it is reaching an optimal cell-to-substrate stiffness value. These in vivo insights on cell-to-substrate mechanical interplay have major implications to our re-interpretation of physiological and pathological contexts.

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Fascin regulates protrusions and delamination to mediate invasive, collective cell migration in vivo

10.1101/734475 ◽

2019 ◽

Cited By ~ 1

Author(s):

Maureen C. Lamb ◽

Kelsey K. Anliker ◽

Tina L. Tootle

Keyword(s):

Cell Migration ◽

Cancer Metastasis ◽

Collective Cell Migration ◽

Nurse Cells ◽

Border Cells ◽

Border Cell ◽

Migration Data ◽

Border Cell Migration

AbstractFascin is an actin bundling protein that is essential for developmental cell migrations and promotes cancer metastasis. In addition to bundling actin, Fascin has several actin-independent roles. Border cell migration during Drosophila oogenesis provides an excellent model to study Fascin’s various roles during invasive, collective cell migration. Border cell migration requires Fascin. Fascin functions not only within the migrating border cells, but also within the nurse cells, the substrate for this migration. Loss of Fascin results in increased, shorter and mislocalized protrusions during migration. Data supports the model that Fascin promotes the activity of Enabled, an actin elongating factor, to regulate migration. Additionally, loss of Fascin inhibits border cell delamination. These defects are partially due to altered E-cadherin localization in the border cells; this is predicted to be an actin-independent role of Fascin. Overall, Fascin is essential for multiple aspects of this invasive, collective cell migration, and functions in both actin-dependent and -independent manners. These findings have implications beyond Drosophila, as border cell migration has emerged as a model to study mechanisms mediating cancer metastasis.

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Roles of leader and follower cells in collective cell migration

Molecular Biology of the Cell ◽

10.1091/mbc.e20-10-0681 ◽

2021 ◽

Vol 32 (14) ◽

pp. 1267-1272

Author(s):

Lei Qin ◽

Dazhi Yang ◽

Weihong Yi ◽

Huiling Cao ◽

Guozhi Xiao

Keyword(s):

Cell Migration ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Cell Movement ◽

Special Focus ◽

Collective Cell Migration ◽

Force Transmission ◽

Collective Movement

Collective cell migration is a widely observed phenomenon during animal development, tissue repair, and cancer metastasis. Considering its broad involvement in biological processes, it is essential to understand the basics behind the collective movement. Based on the topology of migrating populations, tissue-scale kinetics, called the “leader–follower” model, has been proposed for persistent directional collective movement. Extensive in vivo and in vitro studies reveal the characteristics of leader cells, as well as the special mechanisms leader cells employ for maintaining their positions in collective migration. However, follower cells have attracted increasing attention recently due to their important contributions to collective movement. In this Perspective, the current understanding of the molecular mechanisms behind the “leader–follower” model is reviewed with a special focus on the force transmission and diverse roles of leaders and followers during collective cell movement.

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Faculty Opinions recommendation of Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732661919.793542705 ◽

2018 ◽

Author(s):

Ann Sutherland

Keyword(s):

Cell Migration ◽

Collective Cell Migration

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Faculty Opinions recommendation of α-Catenin Controls the Anisotropy of Force Distribution at Cell-Cell Junctions during Collective Cell Migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733465778.793561842 ◽

2019 ◽

Author(s):

Johan De Rooij

Keyword(s):

Cell Migration ◽

Cell Junctions ◽

Force Distribution ◽

Collective Cell Migration ◽

Cell Cell

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Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽

10.1242/dev.191767 ◽

2021 ◽

Vol 148 (7) ◽

pp. dev191767

Author(s):

Jessica Stock ◽

Andrea Pauli

Keyword(s):

Cell Migration ◽

Multiple Scales ◽

Single Cells ◽

Cell Movement ◽

Biological Response ◽

Collective Cell Migration ◽

Theoretical Concepts ◽

Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

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