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Keywords = amoeboid movement

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14 pages, 2397 KB  
Article
Revisiting Chirality in Slime Mold: On the Emergence and Absence of Lateralized Movement in Physarum polycephalum Influenced by Various Stimuli
by Rowena Gehrke and Jannes Freiberg
Symmetry 2025, 17(5), 756; https://doi.org/10.3390/sym17050756 - 14 May 2025
Viewed by 1108
Abstract
Behavioral lateralization in animals is a well-known phenomenon; however, it has only rarely been studied in unicellular organisms. A groundbreaking study found lateralized movement in T-mazes in the formless plasmodia of the slime mold Physarum polycephalum. In this work, a replication of [...] Read more.
Behavioral lateralization in animals is a well-known phenomenon; however, it has only rarely been studied in unicellular organisms. A groundbreaking study found lateralized movement in T-mazes in the formless plasmodia of the slime mold Physarum polycephalum. In this work, a replication of that study was conducted in a specially designed, elaborated T-maze system. Considering the amoeboid organism’s diverse sensory capabilities, we further comprehensively investigated the influence of light, artificial magnetic fields, the magnetic field of the Earth, and vibration on movement direction. Two different clonal lines were tested to assess genetic diversity, encompassing over 1600 individual plasmodia. Our results show that no general lateralized behavior exists in the absence of stimuli in both clonal lines. On the other hand, Physarum’s sensitivity to strong magnetic fields and vibration induces significant true lateralization in previously nonlateralized plasmodia (37.6% right and 62.4% left, respectively). Possible mechanisms behind this induced lateralization are discussed. We conclude that previous findings showing lateralization are likely to have been influenced by unknown external stimuli. Full article
(This article belongs to the Section Life Sciences)
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13 pages, 2836 KB  
Article
Morphokinetic Behavior of the Second Polar Body in Human Zygotes as a Predictor for Embryonic Developmental Potential: An Exploratory Study Based on Time-Lapse Observation
by Toko Shimura, Panagiota Tsounapi, Keitaro Yumoto and Yasuyuki Mio
Int. J. Mol. Sci. 2025, 26(7), 3190; https://doi.org/10.3390/ijms26073190 - 29 Mar 2025
Viewed by 917
Abstract
Time-lapse imaging has made possible the detailed observation of all stages of embryonic development, including also from the extrusion of the second polar body up to the first cleavage. By extensive observation, we achieved detection of a variety of behaviors of PBIIs such [...] Read more.
Time-lapse imaging has made possible the detailed observation of all stages of embryonic development, including also from the extrusion of the second polar body up to the first cleavage. By extensive observation, we achieved detection of a variety of behaviors of PBIIs such as (a) morphologically static behavior, (b) amoeboid movement, (c) shrinking, (d) fragmenting, and (e) ruffling. Retrospective analysis was performed on 282 ICSI zygotes derived from 69 ART treatment cycles from January to August 2019. Zygotes with morphologically static PBIIs (a) and PBIIs showing various behaviors (b)~(e) were classified into Group 1 (n = 70) and Group 2 (n = 212), respectively. Based on the rates of irregular division, good quality embryos, and the time from the PBII extrusion, pronuclear breakdown to the first cleavage was compared between groups (Study 1). Furthermore, the relationship between the type of PBII behaviors and ploidy in 94 biopsied blastocysts from 15 cycles was examined, in which one or more euploid embryos were obtained between August 2021 and July 2024 (Study 2). The results showed that good quality embryos tended to have morphologically static PBIIs, and that euploid embryos were absent in embryos with fragmenting and ruffling PBIIs. The behavior of PBIIs may be a new predictor of embryonic developmental potential, and, in the future, morphokinetic behaviors of PBIIs may be a useful parameter for AI-assisted embryo evaluation systems. Full article
(This article belongs to the Special Issue Molecular Research on Embryo Developmental Potential)
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21 pages, 4485 KB  
Article
From Molecules to Amoeboid Movement: A New Way for Understanding the Morphology Through Actin-Binding Proteins
by Ekaterina Volkova, Igor Pozdnyakov, Mikhail Petukhov and Valeriia Polezhaeva
Biomolecules 2024, 14(12), 1583; https://doi.org/10.3390/biom14121583 - 11 Dec 2024
Viewed by 1284
Abstract
Amoebozoa is a group of single-celled organisms that change their shape during locomotion. However, there is a taxon-specific complex of morphological characters inherent in the moving amoebae, known as locomotive forms. Actin is one of the proteins most important for amoeboid movement that, [...] Read more.
Amoebozoa is a group of single-celled organisms that change their shape during locomotion. However, there is a taxon-specific complex of morphological characters inherent in the moving amoebae, known as locomotive forms. Actin is one of the proteins most important for amoeboid movement that, together with actin-binding proteins, construct the architecture of the cytoskeleton in the amoeboid cells. One of the actin-binding proteins is the Arp2/3 complex that provides a connection between actin filaments at an angle of 70°. In this paper, we predicted 3D models of bonded subunits Arp2 and Arp3 for 30 species from different taxa of Amoebozoa based on the publicly available transcriptomic data. Moreover, we predicted the binding free energy (ΔG) of bonded subunits Arp2 and Arp3 for 30 species and tried to link it to the morphology of the locomotive forms of amoebae. The ΔG values are the lowest in amoebae with the broad hyaline area, like Vannella spp. Amoebae that produce thin hyaline projections, like Vexillifera abyssalis, are characterized by intermediate ΔG values. Finally, the highest ΔG values are typical for the group of amoebae that have no conspicuous hyaline areas of the cytoplasm, like Pelomyxa shiedti, or have small hyaline caps, like Arcella intermedia. The presented analysis provides new insights into the molecular mechanisms of shape formation in amoeboid cells. Full article
(This article belongs to the Section Molecular Structure and Dynamics)
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15 pages, 2329 KB  
Communication
Centrosome Positioning in Migrating Dictyostelium Cells
by Hellen Ishikawa-Ankerhold, Janina Kroll, Dominic van den Heuvel, Jörg Renkawitz and Annette Müller-Taubenberger
Cells 2022, 11(11), 1776; https://doi.org/10.3390/cells11111776 - 29 May 2022
Cited by 6 | Viewed by 7988
Abstract
Directional cell migration and the establishment of polarity play an important role in development, wound healing, and host cell defense. While actin polymerization provides the driving force at the cell front, the microtubule network assumes a regulatory function, in coordinating front protrusion and [...] Read more.
Directional cell migration and the establishment of polarity play an important role in development, wound healing, and host cell defense. While actin polymerization provides the driving force at the cell front, the microtubule network assumes a regulatory function, in coordinating front protrusion and rear retraction. By using Dictyostelium discoideum cells as a model for amoeboid movement in different 2D and 3D environments, the position of the centrosome relative to the nucleus was analyzed using live-cell microscopy. Our results showed that the centrosome was preferentially located rearward of the nucleus under all conditions tested for directed migration, while the nucleus was oriented toward the expanding front. When cells are hindered from straight movement by obstacles, the centrosome is displaced temporarily from its rearward location to the side of the nucleus, but is reoriented within seconds. This relocalization is supported by the presence of intact microtubules and their contact with the cortex. The data suggest that the centrosome is responsible for coordinating microtubules with respect to the nucleus. In summary, we have analyzed the orientation of the centrosome during different modes of migration in an amoeboid model and present evidence that the basic principles of centrosome positioning and movement are conserved between Dictyostelium and human leukocytes. Full article
(This article belongs to the Special Issue Comparative Biology of Microtubule Organization in Eukaryotes)
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18 pages, 6058 KB  
Article
RAS Mediates BET Inhibitor-Endued Repression of Lymphoma Migration and Prognosticates a Novel Proteomics-Based Subgroup of DLBCL through Its Negative Regulator IQGAP3
by Chih-Cheng Chen, Chia-Chen Hsu, Sung-Lin Chen, Po-Han Lin, Ju-Pei Chen, Yi-Ru Pan, Cih-En Huang, Ying-Ju Chen, Yi-Yang Chen, Yu-Ying Wu and Muh-Hwa Yang
Cancers 2021, 13(19), 5024; https://doi.org/10.3390/cancers13195024 - 7 Oct 2021
Cited by 5 | Viewed by 3185
Abstract
Phenotypic heterogeneity and molecular diversity make diffuse large B-cell lymphoma (DLBCL) a challenging disease. We recently illustrated that amoeboid movement plays an indispensable role in DLBCL dissemination and inadvertently identified that the inhibitor of bromodomain and extra-terminal (BET) proteins JQ1 could repress DLBCL [...] Read more.
Phenotypic heterogeneity and molecular diversity make diffuse large B-cell lymphoma (DLBCL) a challenging disease. We recently illustrated that amoeboid movement plays an indispensable role in DLBCL dissemination and inadvertently identified that the inhibitor of bromodomain and extra-terminal (BET) proteins JQ1 could repress DLBCL migration. To explore further, we dissected the impacts of BET inhibition in DLBCL. We found that JQ1 abrogated amoeboid movement of DLBCL cells through both restraining RAS signaling and suppressing MYC-mediated RhoA activity. We also demonstrated that BET inhibition resulted in the upregulation of a GTPase regulatory protein, the IQ motif containing GTPase activating protein 3 (IQGAP3). IQGAP3 similarly exhibited an inhibitory effect on RAS activity in DLBCL cells. Through barcoded mRNA/protein profiling in clinical samples, we identified a specific subgroup of DLBCL tumors with enhanced phosphatidylinositol-3-kinase (PI3K) activity, which led to an inferior survival in these patients. Strikingly, a lower IQGAP3 expression level further portended those with PI3K-activated DLBCL a very dismal outcome. The inhibition of BET and PI3K signaling activity led to effective suppression of DLBCL dissemination in vivo. Our study provides an important insight into the ongoing efforts of targeting BET proteins as a therapeutic approach for DLBCL. Full article
(This article belongs to the Special Issue Molecular Advances in Diffuse Large B-Cell Lymphoma)
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26 pages, 3827 KB  
Review
Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis
by Saima Usman, Naushin H. Waseem, Thuan Khanh Ngoc Nguyen, Sahar Mohsin, Ahmad Jamal, Muy-Teck Teh and Ahmad Waseem
Cancers 2021, 13(19), 4985; https://doi.org/10.3390/cancers13194985 - 5 Oct 2021
Cited by 283 | Viewed by 17697
Abstract
Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis [...] Read more.
Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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23 pages, 3523 KB  
Article
ShcD Binds DOCK4, Promotes Ameboid Motility and Metastasis Dissemination, Predicting Poor Prognosis in Melanoma
by Ewa Aladowicz, Letizia Granieri, Federica Marocchi, Simona Punzi, Giuseppina Giardina, Pier Francesco Ferrucci, Giovanni Mazzarol, Maria Capra, Giuseppe Viale, Stefano Confalonieri, Sara Gandini, Fiorenza Lotti and Luisa Lanfrancone
Cancers 2020, 12(11), 3366; https://doi.org/10.3390/cancers12113366 - 13 Nov 2020
Cited by 8 | Viewed by 3101
Abstract
Metastases are the primary cause of cancer-related deaths. The underlying molecular and biological mechanisms remain, however, elusive, thus preventing the design of specific therapies. In melanomas, the metastatic process is influenced by the acquisition of metastasis-associated mutational and epigenetic traits and the activation [...] Read more.
Metastases are the primary cause of cancer-related deaths. The underlying molecular and biological mechanisms remain, however, elusive, thus preventing the design of specific therapies. In melanomas, the metastatic process is influenced by the acquisition of metastasis-associated mutational and epigenetic traits and the activation of metastatic-specific signaling pathways in the primary melanoma. In the current study, we investigated the role of an adaptor protein of the Shc family (ShcD) in the acquisition of metastatic properties by melanoma cells, exploiting our cohort of patient-derived xenografts (PDXs). We provide evidence that the depletion of ShcD expression increases a spread cell shape and the capability of melanoma cells to attach to the extracellular matrix while its overexpression switches their morphology from elongated to rounded on 3D matrices, enhances cells’ invasive phenotype, as observed on collagen gel, and favors metastasis formation in vivo. ShcD overexpression sustains amoeboid movement in melanoma cells, by suppressing the Rac1 signaling pathway through the confinement of DOCK4 in the cytoplasm. Inactivation of the ShcD signaling pathway makes melanoma cells more sensitive to therapeutic treatments. Consistently, ShcD expression predicts poor outcome in a cohort of 183 primary melanoma patients. Full article
(This article belongs to the Special Issue Advances and Novel Treatment Options in Metastatic Melanoma)
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10 pages, 1242 KB  
Essay
Symmetry Breaking during Cell Movement in the Context of Excitability, Kinetic Fine-Tuning and Memory of Pseudopod Formation
by Peter J.M. van Haastert
Cells 2020, 9(8), 1809; https://doi.org/10.3390/cells9081809 - 30 Jul 2020
Cited by 4 | Viewed by 3003
Abstract
The path of moving eukaryotic cells depends on the kinetics and direction of extending pseudopods. Amoeboid cells constantly change their shape with pseudopods extending in different directions. Detailed analysis has revealed that time, place and direction of pseudopod extension are not random, but [...] Read more.
The path of moving eukaryotic cells depends on the kinetics and direction of extending pseudopods. Amoeboid cells constantly change their shape with pseudopods extending in different directions. Detailed analysis has revealed that time, place and direction of pseudopod extension are not random, but highly ordered with strong prevalence for only one extending pseudopod, with defined life-times, and with reoccurring events in time and space indicative of memory. Important components are Ras activation and the formation of branched F-actin in the extending pseudopod and inhibition of pseudopod formation in the contractile cortex of parallel F-actin/myosin. In biology, order very often comes with symmetry. In this essay, I discuss cell movement and the dynamics of pseudopod extension from the perspective of symmetry and symmetry changes of Ras activation and the formation of branched F-actin in the extending pseudopod. Combining symmetry of Ras activation with kinetics and memory of pseudopod extension results in a refined model of amoeboid movement that appears to be largely conserved in the fast moving Dictyostelium and neutrophils, the slow moving mesenchymal stem cells and the fungus B.d. chytrid. Full article
(This article belongs to the Special Issue Symmetry Breaking in Cells and Tissues)
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13 pages, 2545 KB  
Article
Mammalian Skeletal Muscle Fibres Promote Non-Muscle Stem Cells and Non-Stem Cells to Adopt Myogenic Characteristics
by Taryn Morash, Henry Collins-Hooper, Robert Mitchell and Ketan Patel
Fibers 2017, 5(1), 5; https://doi.org/10.3390/fib5010005 - 23 Jan 2017
Cited by 3 | Viewed by 7735
Abstract
Skeletal muscle fibres are unique cells in large animals, often composed of thousands of post-mitotic nuclei. Following skeletal muscle damage, resident stem cells, called satellite cells, commit to myogenic differentiation and migrate to carry out repair. Satellite stem cells migrate on muscle fibres [...] Read more.
Skeletal muscle fibres are unique cells in large animals, often composed of thousands of post-mitotic nuclei. Following skeletal muscle damage, resident stem cells, called satellite cells, commit to myogenic differentiation and migrate to carry out repair. Satellite stem cells migrate on muscle fibres through amoeboid movement, which relies on dynamic cell membrane extension and retraction (blebbing). It is not known whether blebbing is due to the intrinsic properties of satellite cells, or induced by features of the myofibre surface. Here, we determined the influence of the muscle fibre matrix on two important features of muscle regeneration: the ability to migrate and to differentiate down a myogenic lineage. We show that the muscle fibre is able to induce amoeboid movement in non-muscle stem cells and non-stem cells. Secondly, we show that prolonged co-culture on myofibres caused amniotic fluid stem cells and breast cancer cells to express MyoD, a key myogenic determinant. Finally, we show that amniotic fluid stem cells co-cultured on myofibres are able to fuse and make myotubes that express Myosin Heavy Chain. Full article
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