scholarly journals Protrusive waves guide 3D cell migration along nanofibers

2015 ◽  
Vol 211 (3) ◽  
pp. 683-701 ◽  
Author(s):  
Charlotte Guetta-Terrier ◽  
Pascale Monzo ◽  
Jie Zhu ◽  
Hongyan Long ◽  
Lakshmi Venkatraman ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Body ◽  
Three Dimensional ◽  
Leading Edge ◽  
Cell Types ◽  
Matrix Deformation ◽  
Directional Movement ◽  
Modeling Data ◽  
3D Cell Migration

In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell migration along fibronectin-coated nanofibers is associated with lateral actin-based waves. These cyclical waves have a fin-like shape and propagate up to several hundred micrometers from the cell body, extending the leading edge and promoting highly persistent directional movement. Cells generate these waves through balanced activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways. The waves originate from one major adhesion site at leading end of the cell body, which is linked through actomyosin contractility to another site at the back of the cell, allowing force generation, matrix deformation and cell translocation. By combining experimental and modeling data, we demonstrate that cell migration in a fibrous environment requires the formation and propagation of dynamic, actin based fin-like protrusions.

scholarly journals Nonpolarized signaling reveals two distinct modes of 3D cell migration

2012 ◽  
Vol 197 (3) ◽  
pp. 439-455 ◽  
Author(s):  
Ryan J. Petrie ◽  
Núria Gavara ◽  
Richard S. Chadwick ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Migration ◽  
Intracellular Signaling ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Leading Edge ◽  
Elastic Behavior ◽  
Collagen Gels ◽  
Primary Fibroblasts ◽  
Context Specific ◽  
3D Cell Migration

We search in this paper for context-specific modes of three-dimensional (3D) cell migration using imaging for phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and active Rac1 and Cdc42 in primary fibroblasts migrating within different 3D environments. In 3D collagen, PIP3 and active Rac1 and Cdc42 were targeted to the leading edge, consistent with lamellipodia-based migration. In contrast, elongated cells migrating inside dermal explants and the cell-derived matrix (CDM) formed blunt, cylindrical protrusions, termed lobopodia, and Rac1, Cdc42, and PIP3 signaling was nonpolarized. Reducing RhoA, Rho-associated protein kinase (ROCK), or myosin II activity switched the cells to lamellipodia-based 3D migration. These modes of 3D migration were regulated by matrix physical properties. Specifically, experimentally modifying the elasticity of the CDM or collagen gels established that nonlinear elasticity supported lamellipodia-based migration, whereas linear elasticity switched cells to lobopodia-based migration. Thus, the relative polarization of intracellular signaling identifies two distinct modes of 3D cell migration governed intrinsically by RhoA, ROCK, and myosin II and extrinsically by the elastic behavior of the 3D extracellular matrix.

scholarly journals Computational estimates of mechanical constraints on cell migration through the extracellular matrix

2020 ◽  
Author(s):  
Ondrej Maxian ◽  
Alex Mogilner ◽  
Wanda Strychalski
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Pressure Gradient ◽  
Cell Body ◽  
Fluid Pressure ◽  
Three Dimensional ◽  
Extracellular Fluid ◽  
Cell Cortex ◽  
3D Cell Migration ◽  
Parameter Values

AbstractCell migration through a three-dimensional (3D) extracellular matrix (ECM) underlies important physiological phenomena and is based on a variety of mechanical strategies depending on the cell type and the properties of the ECM. By using computer simulations, we investigate two such migration mechanisms – ‘push-pull’ (forming a finger-like protrusion, adhering to an ECM node, and pulling the cell body forward) and ‘rear-squeezing’ (pushing the cell body through the ECM by contracting the cell cortex and ECM at the cell rear). We present a computational model that accounts for both elastic deformation and forces of the ECM, an active cell cortex and nucleus, and for hydrodynamic forces and flow of the extracellular fluid, cytoplasm and nucleoplasm. We find that relations between three mechanical parameters – the cortex’s contractile force, nuclear elasticity and ECM rigidity – determine the effectiveness of cell migration through the dense ECM. The cell can migrate persistently even if its cortical contraction cannot deform a near-rigid ECM, but then the contraction of the cortex has to be able to sufficiently deform the nucleus. The cell can also migrate even if it fails to deform a stiff nucleus, but then it has to be able to sufficiently deform the ECM. Simulation results show that nuclear stiffness limits the cell migration more than the ECM rigidity. Simulations of the rear-squeezing mechanism of motility results in more robust migration with larger cell displacements than those with the push-pull mechanism over a range of parameter values.Author summaryComputational simulations of models representing two different mechanisms of 3D cell migration in an extracellular matrix are presented. One mechanism represents a mesenchymal mode, characterized by finger-like actin protrusions, while the second mode is more amoeboid in that rear contraction of the cortex propels the cell forward. In both mechanisms, the cell generates a thin actin protrusion on the cortex that attaches to an ECM node. The cell is then either pulled (mesenchymal) or pushed (amoeboid) forward. Results show both mechanisms result in successful migration over a range of simulated parameter values as long as the contractile tension of the cortex exceeds either the nuclear stiffness or ECM stiffness, but not necessarily both. However, the distance traveled by the amoeboid migration mode is more robust to changes in parameter values, and is larger than in simulations of the mesenchymal mode. Additionally cells experience a favorable fluid pressure gradient when migrating in the amoeboid mode, and an adverse fluid pressure gradient in the mesenchymal mode.

scholarly journals Generation of fluorescent cell-derived-matrix to study 3D cell migration

2019 ◽  
Author(s):  
Amélie Luise Godeau ◽  
Hélène Delanoë-Ayari ◽  
Daniel Riveline
Keyword(s):  
Cell Migration ◽  
Flat Surfaces ◽  
Polymeric Networks ◽  
Motile Cells ◽  
Matrix Deformation ◽  
3D Cell Migration ◽  
Cell Motion ◽  
Cellular Forces

AbstractCell migration is involved in key phenomena in biology, ranging from development to cancer. Fibroblasts move between organs in 3D polymeric networks. So far, motile cells were mainly tracked in vitro on Petri dishes or on coverslips, i.e. 2D flat surfaces, which made the extrapolation to 3D physiological environments difficult. We therefore prepared 3D Cell Derived Matrix (CDM) with specific characteristics with the goal of extracting the main readouts required to measure and characterise cell motion: cell specific matrix deformation through the tracking of fluorescent fibronectin within CDM, focal contacts as the cell anchor and acto-myosin cytoskeleton which applies cellular forces. We report our method for generating this assay of physiological-like gel with relevant readouts together with its potential impact in explaining cell motility in vivo.

scholarly journals Dkk-1 Inhibits Intestinal Epithelial Cell Migration by Attenuating Directional Polarization of Leading Edge Cells

2009 ◽  
Vol 20 (22) ◽  
pp. 4816-4825 ◽  
Author(s):  
Stefan Koch ◽  
Christopher T. Capaldo ◽  
Stanislav Samarin ◽  
Porfirio Nava ◽  
Irmgard Neumaier ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Leading Edge ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
Microtubule Organizing Center ◽  
Organizing Center ◽  
Interfering Rna

Wnt signaling pathways regulate proliferation, motility, and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted Wnt antagonist that has been proposed to regulate tissue homeostasis in the intestine. In this report, we show that Dkk-1 is secreted by intestinal epithelial cells after wounding and that it inhibits cell migration by attenuating the directional orientation of migrating epithelial cells. Dkk-1 exposure induced mislocalized activation of Cdc42 in migrating cells, which coincided with a displacement of the polarity protein Par6 from the leading edge. Consequently, the relocation of the microtubule organizing center and the Golgi apparatus in the direction of migration was significantly and persistently inhibited in the presence of Dkk-1. Small interfering RNA-induced down-regulation of Dkk-1 confirmed that extracellular exposure to Dkk-1 was required for this effect. Together, these data demonstrate a novel role of Dkk-1 in the regulation of directional polarization of migrating intestinal epithelial cells, which contributes to the effect of Dkk-1 on wound closure in vivo.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

Nanotopography-Modulated Epithelial Cell Collective Migration

2021 ◽  
Vol 17 (6) ◽  
pp. 1079-1087
Author(s):  
Zaozao Chen ◽  
Qiwei Li ◽  
Shihui Xu ◽  
Jun Ouyang ◽  
Hongmei Wei
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Leading Edge ◽  
Cell Types ◽  
Protein Kinase Activity ◽  
Migration Behavior ◽  
Collective Migration ◽  
Epithelial Migration ◽  
Activity Dependent

Matrix nanotopography plays an essential role in regulating cell behaviors including cell proliferation, differentiation, and migration. While studies on isolated single cell migration along the nanostructural orientation have been reported for various cell types, there remains a lack of understanding of how nanotopography regulates the behavior of collectively migrating cells during processes such as epithelial wound healing. We demonstrated that collective migration of epithelial cells was promoted on nanogratings perpendicular to, but not on those parallel to, the wound-healing axis. We further discovered that nanograting-modulated epithelial migration was dominated by the adhesion turnover process, which was Rho-associated protein kinase activity-dependent, and the lamellipodia protrusion at the cell leading edge, which was Rac1-GTPase activity-dependent. This work provides explanations to the distinct migration behavior of epithelial cells on nanogratings, and indicates that the effect of nanotopographic modulations on cell migration is cell-type dependent and involves complex mechanisms

scholarly journals Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility

2006 ◽  
Vol 176 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Erik Sahai ◽  
Raquel Garcia-Medina ◽  
Jacques Pouysségur ◽  
Emmanuel Vial
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Rho Gtpases ◽  
Rho Kinase ◽  
Cell Movement ◽  
Leading Edge ◽  
Cell Periphery ◽  
Tumor Cell Migration ◽  
Tumor Cell Motility

Rho GTPases participate in various cellular processes, including normal and tumor cell migration. It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions. We report that Smurf1-dependent RhoA degradation in tumor cells results in the down-regulation of Rho kinase (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell periphery. The localized inhibition of contractile forces is necessary for the formation of lamellipodia and for tumor cell motility in 2D tissue culture assays. In 3D invasion assays, and in in vivo tumor cell migration, the inhibition of Smurf1 induces a mesenchymal–amoeboid–like transition that is associated with a more invasive phenotype. Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling.

Tough Double-Network Hydrogels as Scaffolds for Tissue Engineering

2012 ◽  
pp. 213-222
Author(s):  
Jing Jing Yang ◽  
Jian Fang Liu ◽  
Takayuki Kurokawa ◽  
Nobuto Kitamura ◽  
Kazunori Yasuda ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
Cell Types ◽  
Embryoid Bodies ◽  
Living Tissue ◽  
Double Network ◽  
Dimensional Network

Hydrogels are used as scaffolds for tissue engineering in vitro & in vivo because their three-dimensional network structure and viscoelasticity are similar to those of the macromolecular-based extracellular matrix (ECM) in living tissue. Especially, the synthetic hydrogels with controllable and reproducible properties were used as scaffolds to study the behaviors of cells in vitro and implanted test in vivo. In this review, two different structurally designed hydrogels, single-network (SN) hydrogels and double-network (DN) hydrogels, were used as scaffolds. The behavior of two cell types, anchorage-dependent cells and anchorage-independent cells, and the differentiation behaviors of embryoid bodies (EBs) were investigated on these hydrogels. Furthermore, the behavior of chondrocytes on DN hydrogels in vitro and the spontaneous cartilage regeneration induced by DN hydrogels in vivo was examined.

scholarly journals Scribble, Lgl1, and myosin II form a complex in vivo to promote directed cell migration

2020 ◽  
Vol 31 (20) ◽  
pp. 2234-2248
Author(s):  
Maha Abedrabbo ◽  
Shoshana Ravid
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Myosin Ii ◽  
Leading Edge ◽  
Directed Cell Migration ◽  
Lethal Giant Larvae ◽  
And Migration ◽  
Migrating Cells

Here we show that Scribble (Scrib), Lethal giant larvae 1 (Lgl1), and myosin II form a complex in vivo and colocalize at the cell leading edge of migrating cells, and this colocalization is interdependent. Scrib and Lgl1 are required for proper cell adhesion, polarity, and migration.

scholarly journals One-dimensional topography underlies three-dimensional fibrillar cell migration

2009 ◽  
Vol 184 (4) ◽  
pp. 481-490 ◽  
Author(s):  
Andrew D. Doyle ◽  
Francis W. Wang ◽  
Kazue Matsumoto ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Ligand Density ◽  
One Dimensional ◽  
3D Cell Migration ◽  
Striking Contrast

Current concepts of cell migration were established in regular two-dimensional (2D) cell culture, but the roles of topography are poorly understood for cells migrating in an oriented 3D fibrillar extracellular matrix (ECM). We use a novel micropatterning technique termed microphotopatterning (μPP) to identify functions for 1D fibrillar patterns in 3D cell migration. In striking contrast to 2D, cell migration in both 1D and 3D is rapid, uniaxial, independent of ECM ligand density, and dependent on myosin II contractility and microtubules (MTs). 1D and 3D migration are also characterized by an anterior MT bundle with a posterior centrosome. We propose that cells migrate rapidly through 3D fibrillar matrices by a 1D migratory mechanism not mimicked by 2D matrices.

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