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      Cellular velocity, electrical persistence and sensing in developed and vegetative cells during electrotaxis

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          Abstract

          Cells have the ability to detect electric fields and respond to them with directed migratory movement. Investigations identified genes and proteins that play important roles in defining the migration efficiency. Nevertheless, the sensing and transduction mechanisms underlying directed cell migration are still under discussion. We use Dictyostelium discoideum cells as model system for studying eukaryotic cell migration in DC electric fields. We have defined the temporal electric persistence to characterize the memory that cells have in a varying electric field. In addition to imposing a directional bias, we observed that the electric field influences the cellular kinematics by accelerating the movement of cells along their paths. Moreover, the study of vegetative and briefly starved cells provided insight into the electrical sensing of cells. We found evidence that conditioned medium of starved cells was able to trigger the electrical sensing of vegetative cells that would otherwise not orient themselves in the electric field. This observation may be explained by the presence of the conditioned medium factor (CMF), a protein secreted by the cells, when they begin to starve. The results of this study give new insights into understanding the mechanism that triggers the electrical sensing and transduces the external stimulus into directed cell migration. Finally, the observed increased mobility of cells over time in an electric field could offer a novel perspective towards wound healing assays.

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          Most cited references36

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          Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.

          Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.
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            Chemotaxis: signalling the way forward.

            During random locomotion, human neutrophils and Dictyostelium discoideum amoebae repeatedly extend and retract cytoplasmic processes. During directed cell migration--chemotaxis--these pseudopodia form predominantly at the leading edge in response to the local accumulation of certain signalling molecules. Concurrent changes in actin and myosin enable the cell to move towards the stimulus. Recent studies are beginning to identify an intricate network of signalling molecules that mediate these processes, and how these molecules become localized in the cell is now becoming clear.
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              Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis.

              Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation, motility, secretion, and invasion), although their contribution to cancer progression has largely been ignored. The purpose of this study was to investigate voltage-gated Na(+) channel (VGSC) expression and its possible role in human breast cancer. Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC alpha-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCalpha expression and its association with metastasis in vivo. VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Na(v)1.5, in its newly identified "neonatal" splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo. An antibody specific for this form confirmed up-regulation of neonatal Na(v)1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Na(v)1.5 expression and clinically assessed lymph node metastasis. Up-regulation of neonatal Na(v)1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Visualization
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2020
                18 September 2020
                : 15
                : 9
                : e0239379
                Affiliations
                [1 ] Max-Planck Institute for Dynamics and Self-organization, Göttingen, Germany
                [2 ] Institute for Dynamics of Complex Systems, Georg-August-University Göttingen, Göttingen, Germany
                [3 ] Laboratory of Atomic and Solid-State Physics, Cornell University, Ithaca, NY, United States of America
                Peking University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-1781-3767
                Article
                PONE-D-20-11797
                10.1371/journal.pone.0239379
                7500600
                61d9da44-eaf7-4768-846d-d0ba068f270e
                © 2020 Guido et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 April 2020
                : 7 September 2020
                Page count
                Figures: 6, Tables: 0, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004189, Max-Planck-Gesellschaft;
                Award ID: MaxSynBio
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004189, Max-Planck-Gesellschaft;
                Award ID: MaxSynBio
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: MaxSynBio
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: MaxSynBio
                Award Recipient :
                E.B. and I.G. Support from the MaxSynBio Consortium which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society. https://www.maxsynbio.mpg.de/13480/maxsynbio The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical Sciences
                Physics
                Electricity
                Electric Field
                Biology and Life Sciences
                Cell Biology
                Cell Physiology
                Cell Polarity
                Engineering and Technology
                Electronics Engineering
                Electronics
                Electrodes
                Cathodes
                Biology and Life Sciences
                Cell Biology
                Cell Motility
                Cell Migration
                Biology and Life Sciences
                Developmental Biology
                Cell Migration
                Engineering and Technology
                Fluidics
                Microfluidics
                Biology and Life Sciences
                Cell Biology
                Cell Motility
                Cell Migration
                Directed Cell Migration
                Biology and Life Sciences
                Developmental Biology
                Cell Migration
                Directed Cell Migration
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Psychology
                Perception
                Sensory Perception
                Biology and Life Sciences
                Psychology
                Cognitive Psychology
                Perception
                Sensory Perception
                Social Sciences
                Psychology
                Cognitive Psychology
                Perception
                Sensory Perception
                Biology and Life Sciences
                Neuroscience
                Sensory Perception
                Biology and Life Sciences
                Psychology
                Behavior
                Conditioned Response
                Social Sciences
                Psychology
                Behavior
                Conditioned Response
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