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Scientific Reports Sep 2021The high throughput, cost effective and sensitive quantification of cell adhesion strength at the single-cell level is still a challenging task. The adhesion force...
The high throughput, cost effective and sensitive quantification of cell adhesion strength at the single-cell level is still a challenging task. The adhesion force between tissue cells and their environment is crucial in all multicellular organisms. Integrins transmit force between the intracellular cytoskeleton and the extracellular matrix. This force is not only a mechanical interaction but a way of signal transduction as well. For instance, adhesion-dependent cells switch to an apoptotic mode in the lack of adhesion forces. Adhesion of tumor cells is a potential therapeutic target, as it is actively modulated during tissue invasion and cell release to the bloodstream resulting in metastasis. We investigated the integrin-mediated adhesion between cancer cells and their RGD (Arg-Gly-Asp) motif displaying biomimetic substratum using the HeLa cell line transfected by the Fucci fluorescent cell cycle reporter construct. We employed a computer-controlled micropipette and a high spatial resolution label-free resonant waveguide grating-based optical sensor calibrated to adhesion force and energy at the single-cell level. We found that the overall adhesion strength of single cancer cells is approximately constant in all phases except the mitotic (M) phase with a significantly lower adhesion. Single-cell evanescent field based biosensor measurements revealed that at the mitotic phase the cell material mass per unit area inside the cell-substratum contact zone is significantly less, too. Importantly, the weaker mitotic adhesion is not simply a direct consequence of the measured smaller contact area. Our results highlight these differences in the mitotic reticular adhesions and confirm that cell adhesion is a promising target of selective cancer drugs as the vast majority of normal, differentiated tissue cells do not enter the M phase and do not divide.
Topics: Apoptosis; Cell Adhesion; Cell Division; HeLa Cells; Humans
PubMed: 34531409
DOI: 10.1038/s41598-021-97734-1 -
Proceedings of the National Academy of... Jan 2022Living systems propagate by undergoing rounds of cell growth and division. Cell division is at heart a physical process that requires mechanical forces, usually exerted...
Living systems propagate by undergoing rounds of cell growth and division. Cell division is at heart a physical process that requires mechanical forces, usually exerted by assemblies of cytoskeletal polymers. Here we developed a physical model for the ESCRT-III-mediated division of archaeal cells, which despite their structural simplicity share machinery and evolutionary origins with eukaryotes. By comparing the dynamics of simulations with data collected from live cell imaging experiments, we propose that this branch of life uses a previously unidentified division mechanism. Active changes in the curvature of elastic cytoskeletal filaments can lead to filament perversions and supercoiling, to drive ring constriction and deform the overlying membrane. Abscission is then completed following filament disassembly. The model was also used to explore how different adenosine triphosphate (ATP)-driven processes that govern the way the structure of the filament is changed likely impact the robustness and symmetry of the resulting division. Comparisons between midcell constriction dynamics in simulations and experiments reveal a good agreement with the process when changes in curvature are implemented at random positions along the filament, supporting this as a possible mechanism of ESCRT-III-dependent division in this system. Beyond archaea, this study pinpoints a general mechanism of cytokinesis based on dynamic coupling between a coiling filament and the membrane.
Topics: Adenosine Triphosphate; Archaea; Cell Division; Cell Membrane; Cytokinesis; Cytoskeleton; Endosomal Sorting Complexes Required for Transport; Sulfolobus acidocaldarius
PubMed: 34983838
DOI: 10.1073/pnas.2107763119 -
Nucleus (Austin, Tex.) Dec 2019Mitosis and meiosis in higher plants involve significant reconfiguration of the nuclear envelope and the proteins that interact with it. The dynamic series of events... (Review)
Review
Mitosis and meiosis in higher plants involve significant reconfiguration of the nuclear envelope and the proteins that interact with it. The dynamic series of events involves a range of interactions, movement, breakdown, and reformation of this complex system. Recently, progress has been made in identifying and characterizing the protein and membrane interactome that performs these complex tasks, including constituents of the nuclear envelope, the cytoskeleton, nucleoskeleton, and chromatin. This review will present the current understanding of these interactions and advances in knowledge of the processes for the breakdown and reformation of the nuclear envelope during cell divisions in plants.
Topics: Meiosis; Mitosis; Nuclear Envelope; Plant Cells
PubMed: 30879391
DOI: 10.1080/19491034.2019.1587277 -
The EMBO Journal Oct 2020The human retinoblastoma (RB1) protein is a tumor suppressor that negatively regulates cell cycle progression through its interaction with members of the E2F/DP family... (Review)
Review
The human retinoblastoma (RB1) protein is a tumor suppressor that negatively regulates cell cycle progression through its interaction with members of the E2F/DP family of transcription factors. However, RB-related (RBR) proteins are an early acquisition during eukaryote evolution present in plant lineages, including unicellular algae, ancient plants (ferns, lycophytes, liverworts, mosses), gymnosperms, and angiosperms. The main RBR protein domains and interactions with E2Fs are conserved in all eukaryotes and not only regulate the G1/S transition but also the G2/M transition, as part of DREAM complexes. RBR proteins are also important for asymmetric cell division, stem cell maintenance, and the DNA damage response (DDR). RBR proteins play crucial roles at every developmental phase transition, in association with chromatin factors, as well as during the reproductive phase during female and male gametes production and embryo development. Here, we review the processes where plant RBR proteins play a role and discuss possible avenues of research to obtain a full picture of the multifunctional roles of RBR for plant life.
Topics: Asymmetric Cell Division; Cell Division; G2 Phase; Humans; Plant Proteins; Plants; Retinoblastoma Protein; Seeds
PubMed: 32865261
DOI: 10.15252/embj.2020105802 -
Cell Cycle (Georgetown, Tex.) Aug 2021Supernumerary centrioles are frequently observed in diverse types of cancer cells. In this study, we investigated the mechanism underlying the generation of...
Supernumerary centrioles are frequently observed in diverse types of cancer cells. In this study, we investigated the mechanism underlying the generation of supernumerary centrioles during the M phase. We generated the triple knockout (KO) cells and determined the configurations of the centriole during the cell cycle. The triple KO cells exhibited a precocious separation of centrioles and unscheduled centriole assembly in the M phase. Supernumerary centrioles in the triple KO cells were present throughout the cell cycle; however, among all the centrioles, only two maintained an intact composition, including CEP135, CEP192, CEP295 and CEP152. Intact centrioles were formed during the S phase and the rest of the centrioles may be generated during the M phase. M-phase-assembled centrioles lacked the ability to organize microtubules in the interphase; however, a fraction of them may acquire pericentriolar material to organize microtubules during the M phase. Taken together, our work reveals the heterogeneity of the supernumerary centrioles in the triple KO cells. .
Topics: Antigens; Cell Cycle Proteins; Cell Division; Centrioles; Gene Deletion; Gene Knockout Techniques; HeLa Cells; Humans; Mitosis; Nerve Tissue Proteins; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 34233584
DOI: 10.1080/15384101.2021.1950386 -
Microbiological Research Sep 2021Giardia duodenalis is a flagellated protozoan that is responsible for many cases of diarrheal disease worldwide and is characterized by its great divergence from the... (Review)
Review
Giardia duodenalis is a flagellated protozoan that is responsible for many cases of diarrheal disease worldwide and is characterized by its great divergence from the model organisms commonly used in studies of basic cellular processes. The life cycle of Giardia involves an infectious cyst form and a proliferative and mobile trophozoite form. Each Giardia trophozoite has two nuclei and a complex microtubule cytoskeleton that consists of eight flagellar axonemes, basal bodies, the adhesive disc, the funis and the median body. Since the success of Giardia infecting other organisms depends on its ability to divide and proliferate efficiently, Giardia must coordinate its cell division to ensure the duplication and partitioning of both nuclei and the multiple cytoskeletal structures. The purpose of this review is to summarize current knowledge about cell division and its regulation in this protist.
Topics: Cell Division; Cytoskeleton; Giardia lamblia; Microtubules; Mitosis; Protozoan Proteins; Trophozoites
PubMed: 34130067
DOI: 10.1016/j.micres.2021.126807 -
Blood Mar 2022
Topics: Cell Division; Signal Transduction
PubMed: 35357478
DOI: 10.1182/blood.2021012726 -
Development (Cambridge, England) Mar 2024Polyploid cells contain multiple genome copies and arise in many animal tissues as a regulated part of development. However, polyploid cells can also arise due to cell... (Review)
Review
Polyploid cells contain multiple genome copies and arise in many animal tissues as a regulated part of development. However, polyploid cells can also arise due to cell division failure, DNA damage or tissue damage. Although polyploidization is crucial for the integrity and function of many tissues, the cellular and tissue-wide consequences of polyploidy can be very diverse. Nonetheless, many polyploid cell types and tissues share a remarkable similarity in function, providing important information about the possible contribution of polyploidy to cell and tissue function. Here, we review studies on polyploid cells in development, underlining parallel functions between different polyploid cell types, as well as differences between developmentally-programmed and stress-induced polyploidy.
Topics: Animals; Cell Division; DNA Damage; Polyploidy
PubMed: 38415794
DOI: 10.1242/dev.202392 -
Cells Nov 2022Cytokinesis, the conclusive act of cell division, allows cytoplasmic organelles and chromosomes to be faithfully partitioned between two daughter cells. In animal... (Review)
Review
Cytokinesis, the conclusive act of cell division, allows cytoplasmic organelles and chromosomes to be faithfully partitioned between two daughter cells. In animal organisms, its accurate regulation is a fundamental task for normal development and for preventing aneuploidy. Cytokinesis failures produce genetically unstable tetraploid cells and ultimately result in chromosome instability, a hallmark of cancer cells. In animal cells, the assembly and constriction of an actomyosin ring drive cleavage furrow ingression, resulting in the formation of a cytoplasmic intercellular bridge, which is severed during abscission, the final event of cytokinesis. Kinase-mediated phosphorylation is a crucial process to orchestrate the spatio-temporal regulation of the different stages of cytokinesis. Several kinases have been described in the literature, such as cyclin-dependent kinase, polo-like kinase 1, and Aurora B, regulating both furrow ingression and/or abscission. However, others exist, with well-established roles in cell-cycle progression but whose specific role in cytokinesis has been poorly investigated, leading to considering these kinases as "minor" actors in this process. Yet, they deserve additional attention, as they might disclose unexpected routes of cell division regulation. Here, we summarize the role of multifunctional kinases in cytokinesis with a special focus on those with a still scarcely defined function during cell cleavage. Moreover, we discuss their implication in cancer.
Topics: Animals; Cytokinesis; Actomyosin; Cell Division; Phosphorylation; Actin Cytoskeleton
PubMed: 36429067
DOI: 10.3390/cells11223639 -
Nature Communications Jun 2023Cell division is spatiotemporally precisely regulated, but the underlying mechanisms are incompletely understood. In the social bacterium Myxococcus xanthus, the...
Cell division is spatiotemporally precisely regulated, but the underlying mechanisms are incompletely understood. In the social bacterium Myxococcus xanthus, the PomX/PomY/PomZ proteins form a single megadalton-sized complex that directly positions and stimulates cytokinetic ring formation by the tubulin homolog FtsZ. Here, we study the structure and mechanism of this complex in vitro and in vivo. We demonstrate that PomY forms liquid-like biomolecular condensates by phase separation, while PomX self-assembles into filaments generating a single large cellular structure. The PomX structure enriches PomY, thereby guaranteeing the formation of precisely one PomY condensate per cell through surface-assisted condensation. In vitro, PomY condensates selectively enrich FtsZ and nucleate GTP-dependent FtsZ polymerization and bundle FtsZ filaments, suggesting a cell division site positioning mechanism in which the single PomY condensate enriches FtsZ to guide FtsZ-ring formation and division. This mechanism shares features with microtubule nucleation by biomolecular condensates in eukaryotes, supporting this mechanism's ancient origin.
Topics: Tubulin; Biomolecular Condensates; Polymerization; Cell Division; Myxococcus xanthus
PubMed: 37380708
DOI: 10.1038/s41467-023-39513-2