scholarly journals SCHEEPDOG: programming electric cues to dynamically herd large-scale cell migration

Author(s):  
Tom J. Zajdel ◽  
Gawoon Shim ◽  
Linus Wang ◽  
Alejandro Rossello-Martinez ◽  
Daniel J. Cohen

AbstractDirected cell migration is critical across biological processes spanning healing to cancer invasion, yet no existing tools allow real-time interactive guidance over such migration. We present a new bioreactor that harnesses electrotaxis—directed cell migration along electric field gradients—by integrating four independent electrodes under computer control to dynamically program electric field patterns, and hence steer cell migration. Using this platform, we programmed and characterized multiple precise, two-dimensional collective migration maneuvers in renal epithelia and primary skin keratinocyte ensembles. First, we demonstrated on-demand, 90-degree collective turning. Next, we developed a universal electrical stimulation scheme capable of programming arbitrary 2D migration maneuvers such as precise angular turns and migration in a complete circle. Our stimulation scheme proves that cells effectively time-average electric field cues, helping to elucidate the transduction time scales in electrotaxis. Together, this work represents an enabling platform for controlling cell migration with broad utility across many cell types.

2020 ◽  
Vol 31 (20) ◽  
pp. 2234-2248
Author(s):  
Maha Abedrabbo ◽  
Shoshana Ravid

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.


2019 ◽  
Vol 476 (4) ◽  
pp. 705-718 ◽  
Author(s):  
Willow Hight-Warburton ◽  
Maddy Parsons

Abstract Integrins are heterodimeric transmembrane receptors that play an essential role in enabling cells to sense and bind to extracellular ligands. Activation and clustering of integrins leads to the formation of focal adhesions at the plasma membrane that subsequently initiate signalling pathways to control a broad range of functional endpoints including cell migration, proliferation and survival. The α4 and α9 integrins form a small sub-family of receptors that share some specific ligands and binding partners. Although relatively poorly studied compared with other integrin family members, emerging evidence suggests that despite restricted cell and tissue expression profiles, these integrins play a key role in the regulation of signalling pathways controlling cytoskeletal remodelling and migration in both adherent and non-adherent cell types. This review summarises the known shared and specific roles for α4 and α9 integrins and highlights the importance of these receptors in controlling cell migration within both homeostatic and disease settings.


Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 91-97 ◽  
Author(s):  
J. G. Williams ◽  
K. A. Jermyn ◽  
K. T. Duffy

The pDd63 and pDd56 genes encode extracellular matrix proteins which, respectively, surround the migratory slug and mature stalk cells. Both genes are dependent for their expression upon, and rapidly induced by, DIF, the stalk cell inducer. Using these genes as cell-autonomous markers, we have defined three distinct kinds of ‘prestalk’ cells localized to different parts of the anterior region of the slug. At least one, and probably both, prestalk cell types initially differentiates at the base of the aggregate. The most abundant of the two prestalk cell types then migrates into the tip, the precursor of the prestalk zone which arises at the apex of the aggregate. Thus we believe that morphogenesis of the prestalk zone, the primary pattern-forming event in Dictyostelium development, involves a combination of positionally localized differentiation and directed cell migration. To account for the positionally localized differentiation of prestalk cells, we invoke the existence of gradients of the known antagonists of DIF — cAMP and NH3. We further suggest that differences in the motility of pstA and pstB cells might result from differences in their chemotactic responsiveness to cAMP signals propagated from the tip.


2020 ◽  
Vol 6 (5) ◽  
pp. eaay4412 ◽  
Author(s):  
Yue Wu ◽  
Afu Fu ◽  
Gilad Yossifon

Self-propelling micromotors are emerging as a promising micro- and nanoscale tool for single-cell analysis. We have recently shown that the field gradients necessary to manipulate matter via dielectrophoresis can be induced at the surface of a polarizable active (“self-propelling”) metallodielectric Janus particle (JP) under an externally applied electric field, acting essentially as a mobile floating microelectrode. Here, we successfully demonstrated that the application of an external electric field can singularly trap and transport bacteria and can selectively electroporate the trapped bacteria. Selective electroporation, enabled by the local intensification of the electric field induced by the JP, was obtained under both continuous alternating current and pulsed signal conditions. This approach is generic and applicable to bacteria and JP, as well as a wide range of cell types and micromotor designs. Hence, it constitutes an important and novel experimental tool for single-cell analysis and targeted delivery.


2011 ◽  
Vol 22 (22) ◽  
pp. 4302-4311 ◽  
Author(s):  
Miguel A. Moreno-Mateos ◽  
Águeda G. Espina ◽  
Belén Torres ◽  
María M. Gámez del Estal ◽  
Ana Romero-Franco ◽  
...  

Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference–mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Daniel Čapek ◽  
Michael Smutny ◽  
Alexandra-Madelaine Tichy ◽  
Maurizio Morri ◽  
Harald Janovjak ◽  
...  

Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.


2020 ◽  
Vol 11 ◽  
Author(s):  
Elias H. Barriga ◽  
Eric Theveneau

Directed cell migration is essential all along an individual’s life, from embryogenesis to tissue repair and cancer metastasis. Thus, due to its biomedical relevance, directed cell migration is currently under intense research. Directed cell migration has been shown to be driven by an assortment of external biasing cues, ranging from gradients of soluble (chemotaxis) to bound (haptotaxis) molecules. In addition to molecular gradients, gradients of mechanical properties (duro/mechanotaxis), electric fields (electro/galvanotaxis) as well as iterative biases in the environment topology (ratchetaxis) have been shown to be able to direct cell migration. Since cells migrating in vivo are exposed to a challenging environment composed of a convolution of biochemical, biophysical, and topological cues, it is highly unlikely that cell migration would be guided by an individual type of “taxis.” This is especially true since numerous molecular players involved in the cellular response to these biasing cues are often recycled, serving as sensor or transducer of both biochemical and biophysical signals. In this review, we confront literature on Xenopus cephalic neural crest cells with that of other cell types to discuss the relevance of the current categorization of cell guidance strategies. Furthermore, we emphasize that while studying individual biasing signals is informative, the hard truth is that cells migrate by performing a sort of “mixotaxis,” where they integrate and coordinate multiple inputs through shared molecular effectors to ensure robustness of directed cell motion.


2020 ◽  
Author(s):  
Hannah Clancy ◽  
Michal Pruski ◽  
Bing Lang ◽  
Jared Ching ◽  
Colin D. McCaig

AbstractBackground:Electric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signaling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPARγ) agonists. We investigated the effect of electric fields on GBM differentiated and stem cell migration and whether this was affected by treatment with the PPARγ agonist pioglitazone.MethodsPrimary GBM cell lines were cultured as differentiated and glioma stem cells (GSCs) and then exposed to EFs using electrotaxis chambers and imaged with time lapse microscopy. Cells were then treated with varying concentrations of pioglitazone and/or its inhibitor GW9662 and their responses to EFs examined.ResultsWe demonstrated that GBM differentiated and GSCs have opposing preferences for anodal and cathodal migration, respectively. Pioglitazone treatment resulted in significantly decreased directed cell migration in both cell types. Western blot analysis did not demonstrate any change in PPARγ expression with and without exposure to EF.ConclusionsOpposing EF responses in primary GBM differentiated cells and GSCs can be inhibited chemically by pioglitazone, implicating GBM EF modulation as a potential target in preventing tumour recurrence.


2010 ◽  
Vol 28 (9) ◽  
pp. 1625-1631
Author(s):  
Z. H. He ◽  
Z. X. Liu ◽  
T. Chen ◽  
C. Shen ◽  
X. Li ◽  
...  

Abstract. The relationship between the average structure of the inner magnetospheric large-scale electric field and geomagnetic activity levels has been investigated by Double Star TC-1 data for radial distances ρ between 4.5 RE and 12.5 RE and MLT between 18:00 h and 06:00 h from July to October in 2004 and 2005. The sunward component of the electric field decreases monotonically as ρ increases and approaches zero as the distance off the Earth is greater than 10 RE. The dawn-dusk component is always duskward. It decreases at about 6 RE where the ring current is typically observed to be the strongest and shows strong asymmetry with respect to the magnetic local time. Surprisingly, the average electric field obtained from TC-1 for low activity is almost comparable to that observed during moderate activity, which is always duskward at the magnetotail (8 RE~12 RE).


Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1171
Author(s):  
Jens Wittner ◽  
Wolfgang Schuh

Krüppel-like factor 2 (KLF2), a transcription factor of the krüppel-like family, is a key regulator of activation, differentiation, and migration processes in various cell types. In this review, we focus on the functional relevance of KLF2 in immune cell migration and homing. We summarize the key functions of KLF2 in the regulation of chemokine receptors and adhesion molecules and discuss the relevance of the KLF2-mediated control of immune cell migration in the context of immune responses, infections, and diseases.


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