Directed Cell Migration Research Articles

Visible light-responsive hydrogels for cellular dynamics and spatiotemporal viscoelastic regulation

Viscoelastic heterogeneity of matrices plays a pivotal role in cancer cell spreading, migration, and metastasis. However, the creation of viscoelastic platforms with spatial-temporal regulation is hindered by cytotoxicity and short regulation durations. Our research presents a dual mechanism for stress relaxation regulation- both intrinsic and responsive- by incorporating Schiff base bonds and a visible light-responsive thiuram disulfide (TDS) moiety into the hydrogel. Modifying base bonds facilitates a broad spectrum of intrinsic stress relaxation times. At the same time, incorporating the visible light-responsive TDS moiety endows the hydrogel with responsive viscoelastic properties. These properties are characterized by minimal cytotoxicity, spatial-temporal controllability, dose dependency, and reversibility. Utilizing this platform, we demonstrate that ovarian cancer cells exhibit contrasting behaviors in contraction and spreading when subjected to dynamic stress relaxation changes over various time periods. Additionally, we observed a “memory effect” in the cell’s response to alterations in stress relaxation time. We can spatially direct cell migration through viscoelastic heterogeneity, achieved via photopatterning substrates and laser spots. This innovative approach provides a means to regulate the viscoelasticity of hydrogels across a wide range of timescales, thereby opening avenues for more advanced studies into how cells interpret and respond to spatiotemporal viscoelastic signals.

Competing elastic and viscous gradients determine directional cell migration.

Cell migration regulates central life processes including embryonic development, tissue regeneration, and tumor invasion. To establish the direction of migration, cells follow exogenous cues. Durotaxis, the directed cell migration toward elastic stiffness gradients, is the classical example of mechanical taxis. However, whether gradients of the relaxation properties in the extracellular matrix may also induce tactic responses (viscotaxis) is not well understood. Moreover, whether and how durotaxis and viscotaxis interact with each other has never been investigated. Here, we integrate clutch models for cell adhesions with an active gel theory of cell migration to reveal the mechanisms that govern viscotaxis. We show that viscotaxis is enabled by an asymmetric expression of cell adhesions that further polarize the intracellular motility forces to establish the cell front, similar to durotaxis. More importantly, when both relaxation and elastic gradients coexist, durotaxis appears more efficient in controlling directed cell migration, which we confirm with experimental results. However, the presence of opposing relaxation gradients to an elastic one can arrest or shift the migration direction. Our model rationalizes for the first time the mechanisms that govern viscotaxis and its competition with durotaxis through a mathematical model.

The multifaceted role of XCL1 in health and disease.

The chemokine XC motif chemokine ligand 1 (XCL1) is an unusually specialized member of a conserved family of around 50 small, secreted proteins that are best known for their ability to stimulate the directional migration of cells. All chemokines adopt a very similar folded structure that binds a specific G protein-coupled receptor (GPCR), and most chemokines bind extracellular matrix glycosaminoglycans, often in a dimeric or oligomeric form. Owing in part to the lack of a disulfide bond that is conserved in all other chemokines, XCL1 interconverts between two distinct structures with distinct functions. One XCL1 fold resembles the structure of all other chemokines (chemokine fold), while the other does not (alternate fold). The chemokine fold of XCL1 displays high affinity for the GPCR XCR1, while the alternative fold binds GAGs and exhibits antimicrobial activity. Although the canonical role of XCL1 as a CD8+ dendritic cell chemoattractant was defined more than a decade ago, the misconception that XCL1 is a lymphocyte-specific chemoattractant still prevails in the recent literature. This review aims to highlight the structure-guided functions of XCL1 and reclarify its immunological role. In addition, the implications of this metamorphic chemokine in vaccine development and emerging functions in the nervous system will be explored.

Visualization of Apical-Basal Stress Polarity Regulating Directed Cell Migration with a FRET-Based Biosensor.

Intracellular morphological apical-basal polarity, regulated by conserved polarity proteins, plays a crucial role in cell migration and metastasis. In this study, using a genetically encoded Förster resonance energy transfer (FRET) biosensor to visually present the spatiotemporal stress state between the lipid rafts on the membrane and the linked actin, we first provide the evidence for the existence of intrinsic apical-basal stress polarity in tumor cells and demonstrate that this polarity is a prerequisite for the formation of flow-induced front-back stress polarity. Interestingly, our study revealed that the front-back stress polarity disappeared upon the disruption of intrinsic apical-basal stress discrepancy, resulting in a large attenuated cell migration activity reduced from 76.2 ± 3.5% to 10 ± 4.9%. This unexpected discovery not only highlights the significance of apical-basal stress polarity as another factor influencing cell migration but also indicates that the disruption of apical-basal polarity in stress might be a novel therapeutic approach for tumor metastasis.

Polarity and migration of cranial and cardiac neural crest cells: underlying molecular mechanisms and disease implications.

The Neural Crest cells are multipotent progenitor cells formed at the neural plate border that differentiate and give rise to a wide range of cell types and organs. Directional migration of NC cells and their correct positioning at target sites are essential during embryonic development, and defects in these processes results in congenital diseases. The NC migration begins with the epithelial-mesenchymal transition and extracellular matrix remodeling. The main cellular mechanisms that sustain this migration include contact inhibition of locomotion, co-attraction, chemotaxis and mechanical cues from the surrounding environment, all regulated by proteins that orchestrate cell polarity and motility. In this review we highlight the molecular mechanisms involved in neural crest cell migration and polarity, focusing on the role of small GTPases, Heterotrimeric G proteins and planar cell polarity complex. Here, we also discuss different congenital diseases caused by altered NC cell migration.

Divergent endothelial mechanisms drive arteriovenous malformations in Alk1 and SMAD4 loss-of-function.

Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder caused by mutations in the bone morphogenetic protein signaling pathway, leading to arteriovenous malformations. While previously thought to share molecular and cellular dysregulation, this study reveals highly distinct mechanisms depending on whether mutations occur in Alk1 or SMAD4. Loss of SMAD4 enhances endothelial cell responses to flow, including flow-regulated transcription and cell migration against blood flow, causing excessive pruning of capillaries and the formation of single large shunts. Conversely, Alk1 deficiency disrupts endothelial flow responses, including cell polarization and directional migration, leading to a dense vascular network and the persistence of a malformation nidus. In vivo cell population tracking of mutant cells validates unique endothelial cell migration defects. Mosaic cell culture models further illustrate that mutant cells co-opt wild-type cells driving distinct Alk1 or SMAD4 mutant-like behavioral defects. These findings demonstrate that arteriovenous malformations develop through fundamentally different cellular mechanisms based on the specific genetic mutation emphasizing the need for tailored diagnostic and therapeutic strategies.

Spatiotemporal distribution of PKCα, PIP3, Moesin, Cdc42, MARCKS, Scriblle, and Arf6 before directed cell migration in monolayers.

Protein kinase Cα (PKCα) has an important role in directed cell migration. After a mechanical wounding, PKCα rapidly accumulates at cell edges adjacent to the wounded cell and regulates cell migration. However, the proteins downstream of PKCα that mediate directed signaling remain unknown. In this study, we examined the spatiotemporal dynamics of PKCα, PIP3, Moesin, Cdc42, MARCKS, Scribble, and Arf6 before directed migration. After wounding, PIP3, Moesin, and Cdc42 accumulated at the cell edge near the wounded cells later than PKCα. In contrast, MARCKS moved away from the plasma membrane without polarization, and Scribble and Arf6 exhibited no significant translocation. The inhibition of PIP3 suppressed the accumulation of Moesin and Cdc42, suggesting that PIP3 regulates Moesin and Cdc42. In particular, the inhibition of PKCα completely inhibited the translocation of all factors, indicating that PKCα is a central regulator in early signaling after wounding and before directional migration.

The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages

Abstract Macrophages are important mediators of immune responses with critical roles in the recognition and clearance of pathogens, as well as in the resolution of inflammation and wound healing. The neuronal guidance cue SLIT2 has been widely studied for its effects on immune cell functions, most notably directional cell migration. Recently, SLIT2 has been shown to directly enhance bacterial killing by macrophages, but the effects of SLIT2 on inflammatory activation of macrophages are less known. Using RNA sequencing analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, we determined that in murine bone marrow–derived macrophages challenged with the potent proinflammatory mediator lipopolysaccharide (LPS), exposure to the bioactive N-terminal fragment of SLIT2 (NSLIT2) suppressed production of proinflammatory cytokines interleukin (IL)-6 and IL-12 and concurrently increased the anti-inflammatory cytokine IL-10. We found that NSLIT2 inhibited LPS-induced MyD88- and TRIF-mediated signaling cascades and did not inhibit LPS-induced internalization of Toll-like receptor 4 (TLR4), but instead inhibited LPS-induced upregulation of macropinocytosis. Inhibition of macropinocytosis in macrophages attenuated LPS-induced production of proinflammatory IL-6 and IL-12 and concurrently enhanced anti-inflammatory IL-10. Taken together, our results indicate that SLIT2 can selectively modulate macrophage response to potent proinflammatory stimuli, such as LPS, by attenuating proinflammatory activation and simultaneously enhancing anti-inflammatory activity. Our results highlight the role of macropinocytosis in proinflammatory activation of macrophages exposed to LPS. Given that LPS-producing bacteria cause host illness through synergistic direct bacterial infection and excessive LPS-induced systemic inflammation, our work suggests a novel therapeutic role for SLIT2 in combatting the significant morbidity and mortality of patients with Gram-negative bacterial sepsis.

Embryonic Mammary Gland Morphogenesis.

Embryonic mammary gland development unfolds with the specification of bilateral mammary lines, thereafter progressing through placode, bud, and sprout stages before branching morphogenesis. Extensive epithelial-mesenchymal interactions guide morphogenesis from embryogenesis to adulthood. Two distinct mesenchymal tissues are involved, the primary mammary mesenchyme that harbors mammary inductive capacity, and the secondary mesenchyme, the precursor of the adult stroma. Placode and bud stages are morphologically similar with other ectodermal appendages like the hair follicle, reflecting the mammary gland's assumed evolutionary origin from an ancestral hair follicle-associated glandular unit. The shared features extend to signalling cascades such as the Wnt/β-catenin, fibroblast growth factor (Fgf), and ectodysplasin (Eda) pathways, while pathways unique to mammary gland include parathyroid hormone-like hormone (Pthlh) signalling and Hedgehog activity suppression. Mammary gland branching is highly non-stereotypic, achieved by the dynamic use of two distinct modes of branching: tip bifurcation and side branching and stochastic branch point formation. The cellular mechanisms driving the initial morphogenetic steps are slowly beginning to be unravelled. During placode and bud stages, mammary primordium predominantly grows through cell influx, while sprouting correlates with heightened proliferation. Branch elongation is driven by directional cell migration combined with differential cell motility and proliferation supplying the reservoir of migratory cells, whereas a bifurcating tip is associated with localized repression of the cell cycle and cell motility. Numerous similarities exist between embryonic programs and breast tumorigenesis, spanning cellular plasticity, epithelial-stromal interactions, and molecular regulators. Understanding embryonic mammogenesis may provide insights into how normal developmental processes can go awry, leading to malignancy, or how they can be reversed to prevent cancer progression.

The Electric Field Guided HaCaT Cell Migration Through the EGFR/p38 MAPK/Akt Pathway.

Previous studies have shown that the endogenous electric field (EF) is an overriding cure in guiding cell migration toward the wound center to promote wound healing, but the mechanism underlying is unclear. In this study, we investigated the molecular mechanism of electric field-guided cell migration in human keratinocyte HaCaT cells. Our results showed that HaCaT cells migrate toward the anode under EFs. The phosphorylation levels of p38 MAPK and Akt were obviously elevated in the EF. Knocking down p38 MAPK obviously abolished directed migration of HaCaT cells under the EFs. Inhibiting p38 MAPK by SB203580 impaired the EF-guided cell migration. The electric field may guide HaCaT cell migration through the EGFR/p38 MAPK/Akt pathway.

Optogenetically Induced Microtubule Acetylation Unveils the Molecular Dynamics of Actin-Microtubule Crosstalk in Directed Cell Migration.

Microtubule acetylation is implicated in regulating cell motility, yet its physiological role in directional migration and the underlying molecular mechanisms have remained unclear. This knowledge gap has persisted primarily due to a lack of tools capable of rapidly manipulating microtubule acetylation in actively migrating cells. To overcome this limitation and elucidate the causal relationship between microtubule acetylation and cell migration, we developed a novel optogenetic actuator, optoTAT, which enables precise and rapid induction of microtubule acetylation within minutes in live cells. Using optoTAT, we observed striking and rapid responses at both molecular and cellular level. First, microtubule acetylation triggers release of the RhoA activator GEF-H1 from sequestration on microtubules. This release subsequently enhances actomyosin contractility and drives focal adhesion maturation. These subcellular processes collectively promote sustained directional cell migration. Our findings position GEF-H1 as a critical molecular responder to microtubule acetylation in the regulation of directed cell migration, revealing a dynamic crosstalk between the actin and microtubule cytoskeletal networks.

Long range juxtacrine signalling through cadherin for collective cell orientation

Many life phenomena, such as development, morphogenesis, tissue remodelling, and wound healing, are often driven by orderly and directional migration of collective cells. However, when cells are randomly oriented or localized disorder exists in orderly oriented collective cells, cell migration cannot occur in an orderly manner although various motion modes such as global rotation and local swirling and/or various motion patterns such as radial pattern and chiral pattern often occur. Therefore, it is important to control cell orientation to ensure the orderly migration of collective cells. Here, we show that it is not force transmission, but juxtacrine signalling through cadherin that plays a critical role in the orientation of collective cells. Surprisingly, juxtacrine signalling for cell orientation reached cells on a plastic dish that were not directly subjected to mechanical stimulation, up to 7 mm away from the actuator. The present study suggests that even weak mechanical stimulation is transmitted in a long range without force transmission through juxtacrine signalling. The long range juxtacrine signalling might play an important role in various life phenomena. Statement of SignificanceJuxtacrine signalling is direct cell-cell contact-dependent signalling, which plays a crucial role in cell behaviors such as mechanosensing, mechanotransduction and collective cell behaviors, however, there is not enough understanding about juxtacrine signalling. The present study has demonstrated that juxtacrine signalling for collective cell orientation is transmitted over a long range through cadherin. To the best of our knowledge, this is the first report of long range juxtacrine signalling. This finding may lead to the elucidation of various life phenomena such as development, morphogenesis, tissue remodelling, and wound healing.

Prognostic Value and Therapeutic Significance of CCL Chemokines in Gastric Cancer.

Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health. CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines. In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer. The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration. These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.

Magnetic Actuation for Mechanomedicine

In the perspective of this article, the emergence of materials and systems for magneto‐mechanical actuation in the field of mechanobiology is presented, and their potential to promote and advance biomedical research is discussed. These materials, ranging from single particles to compliant 2D substrates to 3D scaffolds, enable mechanical modulation of cells in a remote, dynamic, and reversible fashion. These features represent a major advance enabling researchers to reproduce time‐evolving physiological and pathological processes in vitro and transmit mechanical forces and deformations to activate cellular responses or promote directed cell migration. As smart in vitro platforms, magneto‐responsive systems may accelerate the discovery of mechanically mediated cellular mechanisms as therapeutic targets. In addition, the low magnetic susceptibility of biological tissues may facilitate the translation of in vitro approaches to in vivo settings, opening new routes for biomedical applications.

Janus radial nanofiber patch with leak-proof, antimicrobial, and osteogenic integration for skull base reconstruction

During transsphenoidal surgery to remove pituitary adenomas, the structures of the skull base consisting of the dura mater and skull base bones are destroyed, making it crucial to restore the natural structure of the skull base. We crafted a dual-layer Janus fiber membrane utilizing the layer-by-layer electrospinning technique, comprising an osteoblast layer and a leak-proof antimicrobial layer. Specifically, RPG-1%PCPP radially aligned nanofibrous membranes (osteoblasts) can promote directional cell migration and facilitate cellular osteogenic differentiation. TPC nanofibrous membranes (leak-proof antimicrobial layer) can prevent fluid leakage while releasing antimicrobials for resisting bacterial infections. Bacteriostatic tests showed that cefazolin had a good inhibitory ability against both E. coli and S. aureus. RT-PCR showed that radial fiber membrane loaded with PCPP promoted the expression of ALP and BMP-2 genes, thereby promoting osteogenic differentiation of cells. Animal experiments showed that the BV/TV in the TPC/RPG-1%PCPP fiber membrane group was significantly higher than that in the blank group, indicating that TPC/RPG-1%PCPP could promote bone tissue regeneration.

TRPC3-mediated NFATc1 calcium signaling promotes triple negative breast cancer migration through regulating glypican-6 and focal adhesion

Canonical transient receptor potential isoform 3 (TRPC3), a calcium-permeable non-selective cation channel, has been reported to be upregulated in breast cancers and a modulator of cell migration. Calcium-sensitive transcription factor NFATc1, which is important for cell migration, was shown to be frequently activated in triple negative breast cancer (TNBC) biopsy tissues. However, whether TRPC3-mediated calcium influx would activate NFATc1 and affect the migration of TNBC cells, and, if yes, the underlying mechanisms involved, remain to be investigated. By immunostaining followed by confocal microscopy, TNBC lines MDA-MB-231 and BT-549 were both found to express TRPC3 on their plasma membrane while ER+ line MCF-7 and HER2+ line SK-BR3 do not. Blockade of TRPC3 by pharmacological inhibitor Pyr3 or stable knockdown of TRPC3 by lentiviral vector both inhibited cell migration as measured by wound healing assay. Importantly, blocking TRPC3 by Pyr3 or knockdown of TRPC3 both caused the translocation of NFATc1 from the nucleus to the cytosol as revealed by confocal microscopy. Interestingly, NFATc1 was found to bind to the promoter of glypican 6 (GPC6) as determined by chromatin immunoprecipitation assay. Consistently, knockdown of TRPC3 decreased the expression of GPC6 as revealed by western blotting. Moreover, long-term knockdown of GPC6 by lentiviral vector also consistently decreased the migration of TNBC cells. Intriguingly, GPC6 proteins physically interact with vinculin in MDA-MB-231 as determined by co-immunoprecipitation. Blockade of TRPC3, knockdown of TRPC3 or knockdown of GPC6 all induced larger, stabilized actin-bound peripheral focal adhesion (FA) formations in TNBC cells as determined by co-staining of actin and vinculin followed by confocal microscopy. These large, stabilized actin-bound peripheral FAs indicated a defective FA turnover, and were reported to be responsible for impairing directed cell migration. Our results suggest that, in TNBC cells, calcium influx through TRPC3 channel positively regulates NFATc1 nuclear translocation and GPC6 expression, which maintains the dynamics of FA turnover and optimal cell migration. Our study reveals a novel TRPC3-NFATc1-GPC6-vinculin signaling cascade in maintaining the migration of TNBC cells.

A bulk-surface mechanobiochemical modelling approach for single cell migration in two-space dimensions

In this work, we present a mechanobiochemical model for two-dimensional cell migration which couples mechanical properties of the cell cytosol with biochemical processes taking place near or on the cell plasma membrane. The modelling approach is based on a recently developed mathematical formalism of evolving bulk-surface partial differential equations of reaction–diffusion type. We solve these equations using finite element methods within a moving-mesh framework derived from the weak formulation of the evolving bulk-surface PDEs. In the present work, the cell cytosol interior (bulk) dynamics are coupled to the cell membrane (surface) dynamics through non-homogeneous Dirichlet boundary conditions. The modelling approach exhibits both directed cell migration in response to chemical cues as well as spontaneous migration in the absence of such cues. As a by-product, the approach shows fundamental characteristics associated with single cell migration such as: (i) cytosolic and membrane polarisation, (ii) actin dependent protrusions, and (iii) continuous shape deformation of the cell during migration.Cell migration is an ubiquitous process in life that is mainly triggered by the dynamics of the actin cytoskeleton and therefore is driven by both mechanical and biochemical processes. It is a multistep process essential for mammalian organisms and is closely linked to a vast diversity of processes; from embryonic development to cancer invasion. Experimental, theoretical and computational studies have been key to elucidate the mechanisms underlying cell migration. On one hand, rapid advances in experimental techniques allow for detailed experimental measurements of cell migration pathways, while, on the other, computational approaches allow for the modelling, analysis and understanding of such observations. The bulk-surface mechanobiochemical modelling approach presented in this work, set premises to study single cell migration through complex non-isotropic environments in two- and three-space dimensions.

New insight into a simple high-yielding method for the production of fully folded and functional recombinant human CCL5

Chemokines are proteins important for a range of biological processes from cell-directed migration (chemotaxis) to cell activation and differentiation. Chemokine C-C ligand 5 (CCL5) is an important pro-inflammatory chemokine attracting immune cells towards inflammatory sites through interaction with its receptors CCR1/3/5. Recombinant production of large quantities of CCL5 in Escherichia coli is challenging due to formation of inclusion bodies which necessitates refolding, often leading to low recovery of biologically active protein. To combat this, we have developed a method for CCL5 production that utilises the purification of SUMO tagged CCL5 from E. coli SHuffle cells avoiding the need to reform disulfide bonds through inclusion body purification and yields high quantities of CCL5 (~ 25 mg/L). We demonstrated that the CCL5 produced was fully functional by assessing well-established cellular changes triggered by CCL5 binding to CCR5, including receptor phosphorylation and internalisation, intracellular signalling leading to calcium flux, as well as cell migration. Overall, we demonstrate that the use of solubility tags, SHuffle cells and low pH dialysis constitutes an approach that increases purification yields of active CCL5 with low endotoxin contamination for biological studies.

APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs

Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction. In addition, APC counteracts the major MT-stabilizer CLASPs at MT plus ends and promotes directional cell migration via modulating cell adhesion force. Reconstitution experiments demonstrate that APC potentiates KIF2A-induced MT catastrophes and antagonizes the stabilizing effect of CLASP2 in vitro. In summary, APC functions as a positive regulator of MT-destabilizer and a negative regulator of MT-stabilizer to orchestrate MT dynamics.

Galvanin is an electric-field sensor for directed cell migration.

Directed cell migration is critical for the rapid response of immune cells, such as neutrophils, following tissue injury or infection. Endogenous electric fields, generated by the disruption of the transepithelial potential across the skin, help to guide the movement of immune and skin cells toward the wound site. However, the mechanisms by which cells sense these physical cues remain largely unknown. Through a CRISPR-based screen, we identified Galvanin, a previously uncharacterized single-pass transmembrane protein that is required for human neutrophils to change their direction of migration in response to an applied electric field. Our results indicate that Galvanin rapidly relocalizes to the anodal side of a cell on exposure to an electric field, and that the net charge on its extracellular domain is necessary and sufficient to drive this relocalization. The spatial pattern of neutrophil protrusion and retraction changes immediately upon Galvanin relocalization, suggesting that it acts as a direct sensor of the electric field that then transduces spatial information about a cell's electrical environment to the migratory apparatus. The apparent mechanism of cell steering by sensor relocalization represents a new paradigm for directed cell migration.