Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Directing cell migration in continuous microchannels by topographical amplification of natural directional persistence.

ABSTRACT: Discrete micropatterns on biomaterial surfaces can be used to guide the direction of mammalian cell movement by orienting cell morphology. However, guiding cell assembly in three-dimensional scaffolds remains a challenge. Here we demonstrate that the random motions of motile cells can be rectified within continuous microchannels without chemotactic gradients or fluid flow. Our results show that uniform width microchannels with an overhanging zigzag design can induce polarization of NIH3T3 fibroblasts and human umbilical vein endothelial cells by expanding the cell front at each turn. These continuous zigzag microchannels can guide the direction of cell movement even for cells with altered intracellular signals that promote random movement. This approach for directing cell migration within microchannels has important potential implications in the design of scaffolds for tissue engineering.

SUBMITTER: Ko YG

PROVIDER: S-EPMC3591109 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Directing cell migration in continuous microchannels by topographical amplification of natural directional persistence.

Ko Young-Gwang YG Co Carlos C CC Ho Chia-Chi CC

Biomaterials 20121023 2

Discrete micropatterns on biomaterial surfaces can be used to guide the direction of mammalian cell movement by orienting cell morphology. However, guiding cell assembly in three-dimensional scaffolds remains a challenge. Here we demonstrate that the random motions of motile cells can be rectified within continuous microchannels without chemotactic gradients or fluid flow. Our results show that uniform width microchannels with an overhanging zigzag design can induce polarization of NIH3T3 fibrob ...[more]

PMID: 23099064

Similar Datasets

Gradient-free directional cell migration in continuous microchannels.

Project description:Directing cell movements within 3D channels is a key challenge in biomedical devices and tissue engineering. In two dimensions, closely spaced arrays of asymmetric teardrop islands can intermittently polarize cells and sustain their autonomous directional migration with no gradients. However, in 3D microchannels composed of linearly connected teardrop segments, negligibly low directional bias is observed. Rather than adopt teardrop shapes, cells evade morphological polarization by spreading across multiple teardrop segments, only partly filling each. We demonstrate here that cells can be forced to adopt the shape of individual segments by connecting the segments at an angle to minimize cell spreading across multiple segments. The resulting rhythmic polarization leads to significant directional bias for NIH3T3 fibroblasts, epithelial cells, and even cells whose intracellular signalling have been purposely altered to affect lamellipodia extension (Rac1) and cell polarity (Cdc42). This gradient-free approach to directing cell migration in 3D microchannels may find significant applications in tissue scaffolds and cell on a chip devices.

| S-EPMC3921693 | biostudies-literature

Mis-localization of Arp2 mRNA impairs persistence of directional cell migration.

Project description:Arp2/3 complex is an actin polymerization nucleator and localized in the leading protrusions of migrating cells. It has been unclear how this complex is targeted to the protrusions and whether its localization is functionally important. We previously demonstrated that mRNAs encoding for the subunits of the complex were localized in the protrusions of fibroblasts, suggesting a mechanism to target the complex to the protrusions. We here present data demonstrating the importance of Arp2/3 complex mRNA localization in directional cell migration. Using a novel mechanism by which Dia1 mRNA is targeted to the perinuclear endoplasmic reticulum, we redirected the mRNA encoding Arp2, a subunit of the Arp2/3 complex, to the perinuclear region in fibroblasts. Knockdown of Arp2 alone caused dramatic reduction of the complex and resulted in narrow protrusions, increased random cell migration speed and loss of directionality. Rescue with a protrusion-localizing Arp2 mRNA restored normal cell migration behavior, whereas rescue with a mis-localizing Arp2 mRNA failed to restore speed and directionality. These results demonstrate that localization of Arp2/3 complex mRNAs in the leading protrusions is functionally important for directional cell migration.

| S-EPMC3057629 | biostudies-literature

Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells.

Project description:Cell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on plastic substrates, patient cells were insensitive to regulation by extracellular matrix proteins, which increase the speeds of control cells. As well as speed, cell migration is also described by directional persistence, the straightness of movement. The aim of this study was to determine whether directional persistence is dysregulated in schizophrenia patient cells and whether it is modified on extracellular matrix proteins. Directional persistence in patient-derived and control-derived olfactory cells was quantified from automated live-cell imaging of migrating cells. On plastic substrates, patient cells were more persistent than control cells, with straighter trajectories and smaller turn angles. On most extracellular matrix proteins, persistence increased in patient and control cells in a concentration-dependent manner, but patient cells remained more persistent. Patient cells therefore have a subtle but complex phenotype in migration speed and persistence on most extracellular matrix protein substrates compared to control cells. If present in the developing brain, this could lead to altered brain development in schizophrenia.

| S-EPMC8430705 | biostudies-literature

Directional persistence of cell migration coincides with stability of asymmetric intracellular signaling.

Project description:It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts, we observe that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence. We further show that distant hot spots are dynamically and stochastically coupled. These results are indicative of a mechanism by which changes in a cell's direction of migration are determined by a fragile balance of relatively rapid intracellular signaling processes.

| S-EPMC2800965 | biostudies-literature

Linking morphodynamics and directional persistence of T lymphocyte migration.

Project description:T cells play a central role in the adaptive immune response, and their directed migration is essential for homing to sites of antigen presentation. Like neutrophils, T lymphocytes are rapidly moving cells that exhibit amoeboid movement, characterized by a definitive polarity with F-actin concentrated at the front and myosin II elsewhere. In this study, we used total internal reflection fluorescence (TIRF) microscopy to monitor the cells' areas of contact with a surface presenting adhesive ICAM-1 and the chemokine, CXCL12/SDF-1. Our analysis reveals that T-cell migration and reorientation are achieved by bifurcation and lateral separation of protrusions along the leading membrane edge, followed by cessation of one of the protrusions, which acts as a pivot for cell turning. We show that the distribution of bifurcation frequencies exhibits characteristics of a random, spontaneous process; yet, the waiting time between bifurcation events depends on whether or not the pivot point remains on the same side of the migration axis. Our analysis further suggests that switching of the dominant protrusion between the two sides of the migration axis is associated with persistent migration, whereas the opposite is true of cell turning. To help explain the bifurcation phenomenon and how distinct migration behaviours might arise, a spatio-temporal, stochastic model describing F-actin dynamics is offered.

| S-EPMC4424674 | biostudies-literature

Directing cell migration with asymmetric micropatterns.

Project description:This report shows that the direction of polarization of attached mammalian cells determines the direction in which they move. Surfaces micropatterned with appropriately functionalized self-assembled monolayers constrain individual cells to asymmetric geometries (for example, a teardrop); these geometries polarize the morphology of the cell. After electrochemical desorption of the self-assembled monolayers removes these constraints and allows the cells to move across the surface, they move toward their blunt ends.

| S-EPMC545855 | biostudies-other

Effects of topographical guidance cues on osteoblast cell migration.

Project description:Cell migration is a fundamental process that is crucial for many biological functions in the body such as immune responses and tissue regeneration. Dysregulation of this process is associated with cancer metastasis. In this study, polydimethylsiloxane platforms with various topographical features were engineered to explore the influence of guiding patterns on MC3T3-E1 osteoblast cell migration. Focusing on the guiding effects of grating patterns, variations such as etch depth, pattern discontinuity, and bending angles were investigated. In all experiments, MC3T3-E1 cells on patterned surfaces demonstrated a higher migration speed and alignment when compared to flat surfaces. The study revealed that an increase in etch depth from 150 nm to 4.5 μm enhanced cell alignment and elongation along the grating patterns. In the presence of discontinuous elements, cell migration speed was accelerated when compared to gratings of the same etch depth. These results indicated that cell directionality preference was influenced by a high level of pattern discontinuity. On patterns with bends, cells were more inclined to reverse on 45° bends, with 69% of cells reversing at least once, compared to 54% on 135° bends. These results are attributed to cell morphology and motility mechanisms that are associated with surface topography, where actin filament structures such as filopodia and lamellipodia are essential in sensing the surrounding environment and controlling cell displacement. Knowledge of geometric guidance cues could provide a better understanding on how cell migration is influenced by extracellular matrix topography in vivo.

| S-EPMC7672072 | biostudies-literature

Fibroblasts generate topographical cues that steer cancer cell migration.

Project description:Fibroblasts play a fundamental role in tumor development. Among other functions, they regulate cancer cells' migration through rearranging the extracellular matrix, secreting soluble factors, and establishing direct physical contacts with cancer cells. Here, we report that migrating fibroblasts deposit on the substrate a network of tubular structures that serves as a guidance cue for cancer cell migration. Such membranous tubular network, hereafter called tracks, is stably anchored to the substrate in a β5-integrin-dependent manner. We found that cancer cells specifically adhere to tracks by using clathrin-coated structures that pinch and engulf tracks. Tracks thus represent a spatial memory of fibroblast migration paths that is read and erased by cancer cells directionally migrating along them. We propose that fibroblast tracks represent a topography-based intercellular communication system capable of steering cancer cell migration.

| S-EPMC10431708 | biostudies-literature

Rear-polarized Wnt5a-receptor-actin-myosin-polarity (WRAMP) structures promote the speed and persistence of directional cell migration.

Project description:In contrast to events at the cell leading edge, rear-polarized mechanisms that control directional cell migration are poorly defined. Previous work described a new intracellular complex, the Wnt5a-receptor-actomyosin polarity (WRAMP) structure, which coordinates the polarized localization of MCAM, actin, and myosin IIB in a Wnt5a-induced manner. However, the polarity and function for the WRAMP structure during cell movement were not determined. Here we characterize WRAMP structures during extended cell migration using live-cell imaging. The results demonstrate that cells undergoing prolonged migration show WRAMP structures stably polarized at the rear, where they are strongly associated with enhanced speed and persistence of directional movement. Strikingly, WRAMP structures form transiently, with cells displaying directional persistence during periods when they are present and cells changing directions randomly when they are absent. Cells appear to pause locomotion when WRAMP structures disassemble and then migrate in new directions after reassembly at a different location, which forms the new rear. We conclude that WRAMP structures represent a rear-directed cellular mechanism to control directional migration and that their ability to form dynamically within cells may control changes in direction during extended migration.

| S-EPMC5541843 | biostudies-literature

Fibronectin promotes directional persistence in fibroblast migration through interactions with both its cell-binding and heparin-binding domains.

Project description:The precise mechanisms through which insoluble, cell-adhesive ligands induce and regulate directional cell migration remain obscure. We recently demonstrated that elevated surface density of physically adsorbed plasma fibronectin (FN) promotes high directional persistence in fibroblast migration. While cell-FN association through integrins α5β1 and αvβ3 was necessary, substrates that selectively engaged these integrins did not support the phenotype. We here show that high directional persistence necessitates a combination of the cell-binding and C-terminal heparin-binding domains of FN, but does not require the engagement of syndecan-4 or integrin α4β1. FN treatment with various fixation agents indicated that associated changes in fibroblast motility were due to biochemical changes, rather than alterations in its physical state. The nature of the coating determined the ability of fibroblasts to assemble endogenous or exogenous FN, while FN fibrillogenesis played a minor, but significant, role in regulating directionality. Interestingly, knockdown of cellular FN abolished cell motility altogether, demonstrating a requirement for intracellular processes in enabling fibroblast migration on FN. Lastly, kinase inhibition experiments revealed that regulation of cell speed and directional persistence are decoupled. Hence, we have identified factors that render full-length FN a promoter of directional migration and discuss the possible, relevant mechanisms.

| S-EPMC5473823 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data