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Journal ArticleDOI

The role and regulation of blebs in cell migration

01 Oct 2013-Current Opinion in Cell Biology (Curr Opin Cell Biol)-Vol. 25, Iss: 5, pp 582-590
TL;DR: Recent findings relevant for the mechanics of bleb formation and the underlying molecular pathways are summarized and the processes involved in determining the type of protrusion formed by migrating cells, in particular in vivo, in the context of embryonic development are reviewed.
About: This article is published in Current Opinion in Cell Biology.The article was published on 2013-10-01 and is currently open access. It has received 311 citations till now. The article focuses on the topics: Bleb (cell biology) & Hydrostatic pressure.
Citations
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Journal ArticleDOI
TL;DR: The feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro is described and this knowledge is integrated into the current understanding of cellular actin organizations and its physiological roles.
Abstract: Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles.

1,128 citations

Journal ArticleDOI
12 Feb 2015-Cell
TL;DR: It is reported that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype and, Interestingly, transformed cells are more prone to adopt this fast migration mode.

662 citations


Cites background from "The role and regulation of blebs in..."

  • ...Several studies report, for example, that amoeboid migration is often based on a contractile cell rear inducing a retrograde flow in the cell cortex (Heuzé et al., 2013; Paluch and Raz, 2013; Poincloux et al., 2011)....

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  • ...The velocity of amoeboid migration is often higher than that of mesenchymal migration (Panková et al., 2010) and it appears to involve a range of different sub-modes, such as bleb-based migration or gliding (Paluch and Raz, 2013)....

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  • ..., 2010) and it appears to involve a range of different sub-modes, such as bleb-based migration or gliding (Paluch and Raz, 2013)....

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  • ...Several studies report, for example, that amoeboid migration is often based on a contractile cell rear inducing a retrograde flow in the cell cortex (Heuzé et al., 2013; Paluch and Raz, 2013; Poincloux et al., 2011)....

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Journal ArticleDOI
TL;DR: Recent advances in understanding of how Rho GTPases contribute to different types of migration are reviewed, comparing lamellipodium-driven versus bleb-driven migration modes and how cells migrate across the endothelium is described.

619 citations


Cites background from "The role and regulation of blebs in..."

  • ...com components and surrounding cells [5,6]....

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  • ...By contrast, in situations of low adhesion or if cells lack integrins, cells tend to migrate using bleb-based motility [5]....

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Journal ArticleDOI
TL;DR: How the balance between actin filament branching and elongation, and between the positive and negative feedback loops that regulate these activities, determines lamellipodial persistence is highlighted.
Abstract: Membrane protrusions at the leading edge of cells, known as lamellipodia, drive cell migration in many normal and pathological situations. Lamellipodial protrusion is powered by actin polymerization, which is mediated by the actin-related protein 2/3 (ARP2/3)-induced nucleation of branched actin networks and the elongation of actin filaments. Recently, advances have been made in our understanding of positive and negative ARP2/3 regulators (such as the SCAR/WAVE (SCAR/WASP family verprolin-homologous protein) complex and Arpin, respectively) and of proteins that control actin branch stability (such as glial maturation factor (GMF)) or actin filament elongation (such as ENA/VASP proteins) in lamellipodium dynamics and cell migration. This Review highlights how the balance between actin filament branching and elongation, and between the positive and negative feedback loops that regulate these activities, determines lamellipodial persistence. Importantly, directional persistence, which results from lamellipodial persistence, emerges as a critical factor in steering cell migration.

493 citations

Journal ArticleDOI
TL;DR: This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments and draws comparisons between 1D, 2D and 3D migration.
Abstract: Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non-muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration.

487 citations

References
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Journal ArticleDOI
01 May 2008-Nature
TL;DR: It is shown here that functional integrins do not contribute to migration in three-dimensional environments, and these cells migrate by the sole force of actin-network expansion, which promotes protrusive flowing of the leading edge.
Abstract: All metazoan cells carry transmembrane receptors of the integrin family, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment In agreement with this principle, rapidly migrating leukocytes use integrin-mediated adhesion when moving over two-dimensional surfaces As migration on two-dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three-dimensional movement of leukocytes within tissues has remained controversial We studied the interplay between adhesive, contractile and protrusive forces during interstitial leukocyte chemotaxis in vivo and in vitro We ablated all integrin heterodimers from murine leukocytes, and show here that functional integrins do not contribute to migration in three-dimensional environments Instead, these cells migrate by the sole force of actin-network expansion, which promotes protrusive flowing of the leading edge Myosin II-dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus

1,288 citations


"The role and regulation of blebs in..." refers background in this paper

  • ...Indeed, leukocytes devoid of receptors that would support adhesion to the extracellular environment were shown to migrate by squeezing and exerting pushing forces perpendicular to the cell boundary [55 ,56]....

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Journal ArticleDOI
TL;DR: Using a multiparameter tuning model, this work describes how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants—including cell–cell and cell–matrix adhesion, cytoskeletal polarity and stiffness, etc.—interdependently control migration mode and efficiency.
Abstract: Cell migration underlies tissue formation, maintenance, and regeneration as well as pathological conditions such as cancer invasion. Structural and molecular determinants of both tissue environment and cell behavior define whether cells migrate individually (through amoeboid or mesenchymal modes) or collectively. Using a multiparameter tuning model, we describe how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants-including cell-cell and cell-matrix adhesion, cytoskeletal polarity and stiffness, and pericellular proteolysis-interdependently control migration mode and efficiency. Motile cells integrate variable inputs to adjust interactions among themselves and with the matrix to dictate the migration mode. The tuning model provides a matrix of parameters that control cell movement as an adaptive and interconvertible process with relevance to different physiological and pathological contexts.

1,239 citations


"The role and regulation of blebs in..." refers background in this paper

  • ...Control of bleb formation Whereas some cell types appear to generate exclusively either actin polymerization-based protrusions or blebs driven by actomyosin contractility [5 ,6], other cells are capable of switching the mode of protrusion formation in response to properties of the environment and intracellular signaling [27 ,28 ,46,47]....

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  • ...The ability to switch between protrusion types and motility modes has been proposed to facilitate cancer dissemination; switching could indeed allow cells that migrate through complex and changing environments to select the most efficient migration mode for a given environment (reviewed in [8,46,48])....

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Journal ArticleDOI
31 Oct 2008-Cell
TL;DR: It is shown that mesenchymal-type movement in melanoma cells is driven by activation of the GTPase Rac through a complex containing NEDD9, a recently identified melanoma metastasis gene, and DOCK3, a Rac guanine nucleotide exchange factor.

924 citations

Journal ArticleDOI
TL;DR: The ERM proteins (ezrin, radixin and moesin) have a crucial role in organizing membrane domains through their ability to interact with transmembrane proteins and the cytoskeleton and can provide structural links to strengthen the cell cortex and regulate the activities of signal transduction pathways.
Abstract: Specialized membrane domains are an important feature of almost all cells. In particular, they are essential to tissues that have a highly organized cell cortex, such as the intestinal brush border epithelium. The ERM proteins (ezrin, radixin and moesin) have a crucial role in organizing membrane domains through their ability to interact with transmembrane proteins and the cytoskeleton. In doing so, they can provide structural links to strengthen the cell cortex and regulate the activities of signal transduction pathways. Recent studies examining the structure and in vivo functions of ERMs have greatly advanced our understanding of the importance of membrane-cytoskeleton interactions.

899 citations


"The role and regulation of blebs in..." refers background in this paper

  • ...In the same direction, as shown in various cell types, weakening the tethering between the membrane and the cell cortex facilitates bleb formation [10 ,13,18 ,25]....

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Journal ArticleDOI
24 Jun 2011-Cell
TL;DR: Four distinct protrusion methods likely act in concert to move cells through complex environments in vivo and require the coordination of a wide spectrum of signaling molecules and regulators of cytoskeletal dynamics.

894 citations


"The role and regulation of blebs in..." refers background in this paper

  • ...Blebs can thus form as an alternative to, or in combination with lamellipodia (Figure 1), and are a key protrusion type in 3D migration [11]....

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