scholarly journals Multiscale mechanical model for cell division orientation in developing biological systems

2019 ◽  
Author(s):  
B. Leggio ◽  
J. Laussu ◽  
E. Faure ◽  
P. Lemaire ◽  
C. Godin
Keyword(s):  
Cell Division ◽  
Mechanical Energy ◽  
Local Environment ◽  
Energetic Cost ◽  
New Paradigm ◽  
General Behaviour ◽  
Biological Phenomena ◽  
A Cell ◽  
Living Tissues

Developing biological structures are highly complex systems, within which shape dynamics at different places is tightly coordinated. One key process at play during development is the regulation of cell division orientation. In this work, through a reformulation of cell division in terms of its energetic cost, we propose that oriented cell division is one mechanism by which cells can read and react to mechanical forces propagating in a tissue even in the absence of interphase cellular elongation in the direction of these forces. This view reproduces standard geometric division long-axis rules as a special case of a more general behaviour, in which systematic deviations from these rules can emerge. We show that states of anisotropic tension in multicellular systems can be the cause of these deviations, as often experimentally found in living tissues. Our results provide a unifying view on the different intracellular mechanisms at play in orienting cell division: they are processes which minimize energy loss, reflecting a trade-off between local and long-range mechanical signals. The consequences of this competition are explored in simulated tissues and confirmed in vivo during both the development of the pupal epithelium of dorsal thorax in D. melanogaster and the epidermal morphogenesis of ascidian embryos.Author summaryIn this work we reformulate the process of cell division orientation in development as a mechanical-energy optimization. We show that classical rules for division orientation naturally emerge when a cell minimizes the work performed against its local environment. Moreover, when multicellular stress profiles are taken into account, observed systematic violations of these rules are explained in correlation with states of anisotropic tension within the tissue. We confirm our findings experimentally on developing systems imaged with cellular resolution. Our results provide a new paradigm to understand cell division in multicellular contexts and contribute to building a physical view of biological phenomena.

scholarly journals Probing the Catalytic Activity of a Cell Division-Specific Transpeptidase In Vivo with β-Lactams

2003 ◽  
Vol 185 (13) ◽  
pp. 3726-3734 ◽  
Author(s):  
Christian Eberhardt ◽  
Lars Kuerschner ◽  
David S. Weiss
Keyword(s):  
Catalytic Activity ◽  
Cell Division ◽  
Penicillin Binding Protein ◽  
In Vitro System ◽  
New Findings ◽  
Peptidoglycan Cell Wall ◽  
Dividing Cells ◽  
A Cell

ABSTRACT Penicillin-binding protein 3 (PBP3; also called FtsI) is a transpeptidase that catalyzes cross-linking of the peptidoglycan cell wall in the division septum of Escherichia coli. To determine whether the catalytic activity of PBP3 is activated during division, we assayed acylation of PBP3 with three β-lactams (cephalexin, aztreonam, and piperacillin) in growing cells. Acylation of PBP3 with cephalexin, but not aztreonam or piperacillin, appeared to be stimulated by cell division. Specifically, cephalexin acylated PBP3 about 50% faster in a population of dividing cells than in a population of filamentous cells in which division was inhibited by inactivation or depletion of FtsZ, FtsA, FtsQ, FtsW, or FtsN. However, in a simpler in vitro system using isolated membranes, acylation with cephalexin was not impaired by depletion of FtsW or FtsN. A conflicting previous report that the ftsA3(Ts) allele interferes with acylation of PBP3 was found to be due to the presence of a thermolabile PBP3 in the strain used in that study. The new findings presented here are discussed in light of the hypothesis that the catalytic activity of PBP3 is stimulated by interaction(s) with other division proteins. We suggest that there might be allosteric activation of substrate binding.

scholarly journals Tissue fusion over nonadhering surfaces

2015 ◽  
Vol 112 (31) ◽  
pp. 9546-9551 ◽  
Author(s):  
Vincent Nier ◽  
Maxime Deforet ◽  
Guillaume Duclos ◽  
Hannah G. Yevick ◽  
Olivier Cochet-Escartin ◽  
...  
Keyword(s):  
Local Environment ◽  
Free Edge ◽  
Tissue Fusion ◽  
Purse String ◽  
Closure Mechanism ◽  
A Cell ◽  
In Vitro Adhesion ◽  
Simple Stochastic Model

Tissue fusion eliminates physical voids in a tissue to form a continuous structure and is central to many processes in development and repair. Fusion events in vivo, particularly in embryonic development, often involve the purse-string contraction of a pluricellular actomyosin cable at the free edge. However, in vitro, adhesion of the cells to their substrate favors a closure mechanism mediated by lamellipodial protrusions, which has prevented a systematic study of the purse-string mechanism. Here, we show that monolayers can cover well-controlled mesoscopic nonadherent areas much larger than a cell size by purse-string closure and that active epithelial fluctuations are required for this process. We have formulated a simple stochastic model that includes purse-string contractility, tissue fluctuations, and effective friction to qualitatively and quantitatively account for the dynamics of closure. Our data suggest that, in vivo, tissue fusion adapts to the local environment by coordinating lamellipodial protrusions and purse-string contractions.

scholarly journals A Specialized Peptidoglycan Synthase Promotes Salmonella Cell Division inside Host Cells

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Sónia Castanheira ◽  
Juan J. Cestero ◽  
Gadea Rico-Pérez ◽  
Pablo García ◽  
Felipe Cava ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Salmonella Enterica ◽  
Bacterial Pathogens ◽  
Bacterial Cell Division ◽  
Daughter Cells ◽  
Target Organs ◽  
A Cell ◽  
Acidic Environments

ABSTRACT Bacterial cell division has been studied extensively under laboratory conditions. Despite being a key event in the bacterial cell cycle, cell division has not been explored in vivo in bacterial pathogens interacting with their hosts. We discovered in Salmonella enterica serovar Typhimurium a gene absent in nonpathogenic bacteria and encoding a peptidoglycan synthase with 63% identity to penicillin-binding protein 3 (PBP3). PBP3 is an essential cell division-specific peptidoglycan synthase that builds the septum required to separate daughter cells. Since S. Typhimurium carries genes that encode a PBP3 paralog—which we named PBP3SAL—and PBP3, we hypothesized that there are different cell division events in host and nonhost environments. To test this, we generated S. Typhimurium isogenic mutants lacking PBP3SAL or the hitherto considered essential PBP3. While PBP3 alone promotes cell division under all conditions tested, the mutant producing only PBP3SAL proliferates under acidic conditions (pH ≤ 5.8) but does not divide at neutral pH. PBP3SAL production is tightly regulated with increased levels as bacteria grow in media acidified up to pH 4.0 and in intracellular bacteria infecting eukaryotic cells. PBP3SAL activity is also strictly dependent on acidic pH, as shown by beta-lactam antibiotic binding assays. Live-cell imaging microscopy revealed that PBP3SAL alone is sufficient for S. Typhimurium to divide within phagosomes of the eukaryotic cell. Additionally, we detected much larger amounts of PBP3SAL than those of PBP3 in vivo in bacteria colonizing mouse target organs. Therefore, PBP3SAL evolved in S. Typhimurium as a specialized peptidoglycan synthase promoting cell division in the acidic intraphagosomal environment. IMPORTANCE During bacterial cell division, daughter cells separate by a transversal structure known as the division septum. The septum is a continuum of the cell wall and therefore is composed of membrane(s) and a peptidoglycan layer. To date, actively growing bacteria were reported to have only a “cell division-specific” peptidoglycan synthase required for the last steps of septum formation and consequently, essential for bacterial life. Here, we discovered that Salmonella enterica has two peptidoglycan synthases capable of synthesizing the division septum. One of these enzymes, PBP3SAL, is present only in bacterial pathogens and evolved in Salmonella to function exclusively in acidic environments. PBP3SAL is used preferentially by Salmonella to promote cell division in vivo in mouse target organs and inside acidified phagosomes. Our data challenge the concept of only one essential cell division-specific peptidoglycan synthase and demonstrate that pathogens can divide in defined host locations using alternative mechanisms. IMPORTANCE During bacterial cell division, daughter cells separate by a transversal structure known as the division septum. The septum is a continuum of the cell wall and therefore is composed of membrane(s) and a peptidoglycan layer. To date, actively growing bacteria were reported to have only a “cell division-specific” peptidoglycan synthase required for the last steps of septum formation and consequently, essential for bacterial life. Here, we discovered that Salmonella enterica has two peptidoglycan synthases capable of synthesizing the division septum. One of these enzymes, PBP3SAL, is present only in bacterial pathogens and evolved in Salmonella to function exclusively in acidic environments. PBP3SAL is used preferentially by Salmonella to promote cell division in vivo in mouse target organs and inside acidified phagosomes. Our data challenge the concept of only one essential cell division-specific peptidoglycan synthase and demonstrate that pathogens can divide in defined host locations using alternative mechanisms.

scholarly journals Disassembly and degradation of MinD oscillator complexes by Escherichia coli ClpXP

2020 ◽  
Author(s):  
Christopher J. LaBreck ◽  
Catherine E. Trebino ◽  
Colby N. Ferreira ◽  
Josiah J. Morrison ◽  
Eric C. DiBiasio ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Division ◽  
Linear Polymers ◽  
Atp Binding Site ◽  
Ftsz Ring ◽  
Degradation Reactions ◽  
A Cell ◽  
The Mind

AbstractMinD is a cell division ATPase in Escherichia coli that oscillates from pole to pole and regulates the spatial position of the cell division machinery. Together with MinC and MinE, the Min system restricts assembly of the FtsZ-ring to midcell, oscillating between the opposite ends of the cell and preventing FtsZ-ring misassembly at the poles. Here, we show that the ATP-dependent bacterial proteasome complex ClpXP degrades MinD in reconstituted degradation reactions in vitro, through direct recognition of the MinD N-terminal region, and in vivo. MinD degradation is enhanced during stationary phase, suggesting that ClpXP regulates levels of MinD in cells that are not actively dividing. MinC and MinD are known to co-assemble into linear polymers, therefore we monitored copolymers assembled in vitro after incubation with ClpXP and observed that ClpXP promotes rapid MinCD copolymer disassembly as a result of direct MinD degradation by ClpXP. The N-terminus of MinD, including residue Arg 3, which is near the ATP-binding site, is critical for degradation by ClpXP. Together, these results demonstrate that ClpXP degradation modifies conformational assemblies of MinD in vitro and depresses Min function in vivo during periods of reduced proliferation.

scholarly journals Eph-mediated tyrosine phosphorylation of citron kinase controls abscission

2016 ◽  
Vol 214 (5) ◽  
pp. 555-569 ◽  
Author(s):  
Thomas Jungas ◽  
Renaud T. Perchey ◽  
Mohamad Fawal ◽  
Caroline Callot ◽  
Carine Froment ◽  
...  
Keyword(s):  
Cell Division ◽  
Tyrosine Phosphorylation ◽  
Cell Communication ◽  
Local Environment ◽  
Developing Neocortex ◽  
Citron Kinase ◽  
Local Cell ◽  
Communication Pathway

Cytokinesis is the last step of cell division, culminating in the physical separation of daughter cells at the end of mitosis. Cytokinesis is a tightly regulated process that until recently was mostly viewed as a cell-autonomous event. Here, we investigated the role of Ephrin/Eph signaling, a well-known local cell-to-cell communication pathway, in cell division. We show that activation of Eph signaling in vitro leads to multinucleation and polyploidy, and we demonstrate that this is caused by alteration of the ultimate step of cytokinesis, abscission. Control of abscission requires Eph kinase activity, and Src and citron kinase (CitK) are downstream effectors in the Eph-induced signal transduction cascade. CitK is phosphorylated on tyrosines in neural progenitors in vivo, and Src kinase directly phosphorylates CitK. We have identified the specific tyrosine residues of CitK that are phosphorylated and show that tyrosine phosphorylation of CitK impairs cytokinesis. Finally, we show that, similar to CitK, Ephrin/Eph signaling controls neuronal ploidy in the developing neocortex. Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis.

scholarly journals Increasing Brain Permeability of PHA-767491, a Cell Division Cycle 7 Kinase Inhibitor, with Biodegradable Polymeric Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 180
Author(s):  
Elisa Rojas-Prats ◽  
Carlota Tosat-Bitrián ◽  
Loreto Martínez-González ◽  
Vanesa Nozal ◽  
Daniel I. Pérez ◽  
...  
Keyword(s):  
Cell Division ◽  
Kinase Inhibitor ◽  
Polymeric Nanoparticles ◽  
Plga Nanoparticles ◽  
Cell Division Cycle ◽  
Interesting Approach ◽  
A Cell ◽  
Cell Division Cycle 7

A potent cell division cycle 7 (CDC7) kinase inhibitor, known as PHA-767491, has been described to reduce the transactive response DNA binding protein of 43 KDa (TDP-43) phosphorylation in vitro and in vivo, which is one of the main proteins found to aggregate and accumulate in the cytoplasm of motoneurons in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. However, the main drawback of this compound is its low permeability to the central nervous system (CNS), limiting its use for the treatment of neurological conditions. In this context, the use of drug delivery systems like nanocarriers has become an interesting approach to improve drug release to the CNS. In this study, we prepared and characterized biodegradable nanoparticles in order to encapsulate PHA-767491 and improve its permeability to the CNS. Our results demonstrate that poly (lactic-co-glycolic acid) (PLGA) nanoparticles with an average radius between 145 and 155 nm could be used to entrap PHA-767491 and enhance the permeability of this compound through the blood–brain barrier (BBB), becoming a promising candidate for the treatment of TDP-43 proteinopathies such as ALS.

scholarly journals The nucleoid occlusion protein SlmA is a direct transcriptional activator of chitobiose utilization in Vibrio cholerae

2017 ◽  
Author(s):  
Catherine A. Klancher ◽  
Chelsea A. Hayes ◽  
Ankur B. Dalia
Keyword(s):  
Cell Division ◽  
Vibrio Cholerae ◽  
Transcriptional Activation ◽  
Aquatic Environment ◽  
Point Mutations ◽  
Marine Zooplankton ◽  
Contaminated Food ◽  
A Cell

ABSTRACTChitin utilization by the cholera pathogen Vibrio cholerae is required for its persistence and evolution via horizontal gene transfer in the marine environment. Genes involved in the uptake and catabolism of the chitin disaccharide chitobiose are encoded by the chb operon. The orphan sensor kinase ChiS is critical for regulation of this locus, however, the mechanisms downstream of ChiS activation that result in expression of the chb operon are poorly understood. Using an unbiased transposon mutant screen, we uncover that the nucleoid occlusion protein SlmA is a regulator of the chb operon. SlmA has not previously been implicated in gene regulation. Also, SlmA is a member of the TetR family of proteins, which are generally transcriptional repressors. In vitro, we find that SlmA binds directly to the chb operon promoter, and in vivo, we show that this interaction is, surprisingly, required for transcriptional activation of this locus and for chitobiose utilization. Using point mutations that disrupt distinct functions of SlmA, we find that DNA-binding, but not nucleoid occlusion, is critical for transcriptional activation. This study identifies a novel role for SlmA as a transcriptional regulator in V. cholerae in addition to its established role as a cell division licensing factor.AUTHOR SUMMARYThe cholera pathogen Vibrio cholerae is a natural resident of the aquatic environment and causes disease when ingested in the form of contaminated food or drinking water. In the aquatic environment, the shells of marine zooplankton, which are primarily composed of chitin, serve as an important food source for this pathogen. The genes required for the utilization of chitin are tightly regulated in V. cholerae, however, the exact mechanism underlying this regulation is currently unclear. Here, we uncover that a protein involved in regulating cell division is also important for regulating the genes involved in chitin utilization. This is a newly identified property for this cell division protein and the significance of a common regulator for these two disparate activities remains to be understood.

scholarly journals THz irradiation inhibits cell division by affecting actin dynamics

2021 ◽  
Author(s):  
shota yamazaki ◽  
Yuya Ueno ◽  
Ryosuke Hosoki ◽  
Takanori Saito ◽  
Toshitaka Idehara ◽  
...  
Keyword(s):  
Cell Division ◽  
Actin Polymerization ◽  
Time Lapse ◽  
Actin Dynamics ◽  
Filamentous Actin ◽  
Contractile Ring ◽  
Biological Phenomena ◽  
Underlying Mechanisms

Biological phenomena induced by terahertz (THz) irradiation are described in recent reports, but underlying mechanisms, structural and dynamical change of specific molecules are still unclear. In this paper, we performed time-lapse morphological analysis of human cells and found that THz irradiation halts cell division at cytokinesis. At the end of cytokinesis, the contractile ring, which consists of filamentous actin (F-actin), needs to disappear; however, it remained for 1 hour under THz irradiation. Induction of the functional structures of F-actin was also observed in interphase cells. Similar phenomena were also observed under chemical treatment (jasplakinolide), indicating that THz irradiation assists actin polymerization. We previously reported that THz irradiation enhances the polymerization of purified actin in vitro; our current work shows that it increases cytoplasmic F-actin in vivo. Thus, we identified one of the key biomechanisms affected by THz waves.

scholarly journals THz irradiation inhibits cell division by affecting actin dynamics

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0248381
Author(s):  
Shota Yamazaki ◽  
Yuya Ueno ◽  
Ryosuke Hosoki ◽  
Takanori Saito ◽  
Toshitaka Idehara ◽  
...  
Keyword(s):  
Cell Division ◽  
Actin Polymerization ◽  
Time Lapse ◽  
Actin Dynamics ◽  
Filamentous Actin ◽  
Contractile Ring ◽  
Biological Phenomena ◽  
Underlying Mechanisms

Biological phenomena induced by terahertz (THz) irradiation are described in recent reports, but underlying mechanisms, structural and dynamical change of specific molecules are still unclear. In this paper, we performed time-lapse morphological analysis of human cells and found that THz irradiation halts cell division at cytokinesis. At the end of cytokinesis, the contractile ring, which consists of filamentous actin (F-actin), needs to disappear; however, it remained for 1 hour under THz irradiation. Induction of the functional structures of F-actin was also observed in interphase cells. Similar phenomena were also observed under chemical treatment (jasplakinolide), indicating that THz irradiation assists actin polymerization. We previously reported that THz irradiation enhances the polymerization of purified actin in vitro; our current work shows that it increases cytoplasmic F-actin in vivo. Thus, we identified one of the key biomechanisms affected by THz waves.

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