Continuum Modeling of Biological Tissue Growth by Cell Division

2009 ◽  
Author(s):  
Gerard A. Ateshian ◽  
Kevin D. Costa ◽  
Evren U. Azeloglu ◽  
Barclay Morrison ◽  
Clark T. Hung
Keyword(s):  
Cell Division ◽  
Biological Tissue ◽  
Essential Elements ◽  
Tissue Growth ◽  
Tissue Response ◽  
Solid Matrix ◽  
Continuum Modeling ◽  
Daughter Cells ◽  
A Cell ◽  
Osmotic Effects

A framework is formulated for continuum modeling of biological tissue growth that explicitly addresses cell division, using a homogenized representation of cells and the extracellular matrix (ECM). The essential elements of this model rely on the description of the cell as containing a solution of water and osmolytes, and having osmotically inactive solid constituents that may be generically described as a porous solid matrix. The division of a cell into two nearly identical daughter cells normally starts with the duplication of cell contents during the synthesis phase, followed by cell division during the mitosis phase. Thus, ultimately, cell division is equivalent to doubling of the cell solid matrix and osmolyte content, and a resulting increase in water uptake via osmotic effects. In a homogenized representation of the tissue, the geometry of individual cells is not modeled explicitly, but their solid matrix and intracellular osmolyte content can be suitably incorporated into the analysis of the tissue response, thereby accounting for their osmotic effects. Thus, cell division can be described by the growth of these cell constituents, including the accumulation of osmotically active content, and the resultant uptake of water.

scholarly journals Continuum Modeling of Biological Tissue Growth by Cell Division, and Alteration of Intracellular Osmolytes and Extracellular Fixed Charge Density

2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Gerard A. Ateshian ◽  
Kevin D. Costa ◽  
Evren U. Azeloglu ◽  
Barclay Morrison ◽  
Clark T. Hung
Keyword(s):  
Cell Division ◽  
Charge Density ◽  
Water Uptake ◽  
Biological Tissue ◽  
Tissue Growth ◽  
Fixed Charge ◽  
Solid Matrix ◽  
Continuum Modeling ◽  
Fixed Charge Density ◽  
Osmotic Effects

A framework is formulated within the theory of mixtures for continuum modeling of biological tissue growth that explicitly addresses cell division, using a homogenized representation of cells and their extracellular matrix (ECM). The model relies on the description of the cell as containing a solution of water and osmolytes, and having a porous solid matrix. The division of a cell into two nearly identical daughter cells is modeled as the doubling of the cell solid matrix and osmolyte content, producing an increase in water uptake via osmotic effects. This framework is also generalized to account for the growth of ECM-bound molecular species that impart a fixed charge density (FCD) to the tissue, such as proteoglycans. This FCD similarly induces osmotic effects, resulting in extracellular water uptake and osmotic pressurization of the ECM interstitial fluid, with concomitant swelling of its solid matrix. Applications of this growth model are illustrated in several examples.

The asymptotic behaviour of an invasion process

1977 ◽  
Vol 14 (3) ◽  
pp. 584-590 ◽  
Author(s):  
F. P. Kelly
Keyword(s):  
Cell Division ◽  
Asymptotic Behaviour ◽  
The Other ◽  
Adjacent Cell ◽  
Rectangular Lattice ◽  
Parent Cell ◽  
Invasion Process ◽  
Black And White ◽  
Daughter Cells ◽  
A Cell

Black and white cells are positioned at the vertices of a rectangular lattice. When a cell division occurs, the daughter cells are of the same colour as the parent cell; one of them replaces an adjacent cell and the other remains in the position of the parent cell. In one variant of the model it is assumed that whenever a white cell appears at the origin it is transformed into a black cell; apart from this the black and white cells are equally competitive and in particular they divide at the same rate. Initially, only the cell at the origin is black. The asymptotic behaviour of the black clone is investigated.

scholarly journals Scaling morphogen gradients during tissue growth by a cell division rule

Development ◽  
2014 ◽  
Vol 141 (10) ◽  
pp. 2150-2156 ◽  
Author(s):  
I. Averbukh ◽  
D. Ben-Zvi ◽  
S. Mishra ◽  
N. Barkai
Keyword(s):  
Cell Division ◽  
Tissue Growth ◽  
Morphogen Gradients ◽  
Division Rule ◽  
A Cell

scholarly journals Cytokinesis in Eukaryotic Cells: The Furrow Complexity at a Glance

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 271 ◽  
Author(s):  
Roberta Fraschini
Keyword(s):  
Cell Division ◽  
Asymmetric Cell Division ◽  
Animal Cell ◽  
Genetic Material ◽  
Model Organism ◽  
Complex Phase ◽  
Daughter Cells ◽  
Viable Cells ◽  
A Cell ◽  
Duplication Cycle

The duplication cycle is the fascinating process that, starting from a cell, results in the formation of two daughter cells and it is essential for life. Cytokinesis is the final step of the cell cycle, it is a very complex phase, and is a concert of forces, remodeling, trafficking, and cell signaling. All of the steps of cell division must be properly coordinated with each other to faithfully segregate the genetic material and this task is fundamental for generating viable cells. Given the importance of this process, molecular pathways and proteins that are involved in cytokinesis are conserved from yeast to humans. In this review, we describe symmetric and asymmetric cell division in animal cell and in a model organism, budding yeast. In addition, we illustrate the surveillance mechanisms that ensure a proper cell division and discuss the connections with normal cell proliferation and organs development and with the occurrence of human diseases.

Secreted Mediators of Self-Renewal of Hematopoietic Stem Cells Identified Using Bio-Informatic Analysis of Co-Cultures of HSC and Stromal Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2353-2353
Author(s):  
Baiba Vilne ◽  
Rouzanna Istvanffy ◽  
Christina Eckl ◽  
Franziska Bock ◽  
Olivia Prazeres da Costa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Division ◽  
Hematopoietic Stem Cells ◽  
Stromal Cells ◽  
Tissue Growth ◽  
Functional Enrichment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
A Cell

Abstract Abstract 2353 Hematopoiesis is maintained throughout life by the constant production of mature blood cells from hematopoietic stem cells (HSC). One mechanism by which the number of HSC is maintained is self-renewal, a cell division in which at least one of the daughter cells is a cell with the same functional potential as the mother cell. The mechanisms of this process are largely unknown. We have described cell lines that maintain self-renewal in culture. To study possible mechanisms and mediators involved in self-renewal, we performed co-cultures of HSC model cells: Lineage-negative Sca-1+ c-Kit+ (LSK) cells and HSC maintaining UG26–1B6 stromal cells. Microarray analyses were performed on cells prior to co-culture and cells sorted from the cultures. STEM clustering analysis of the data revealed that most changes in gene expression were due to early cell activation. Functional enrichment analysis revealed dynamic changes in focal adhesion and mTOR signaling, as well as changes in epigenetic regulators, such as HDAC in stromal cells. In LSK cells, genes whose products are involved in inflammation, Oxygen homeostasis and metabolism were differentially expressed after the co-culture. In addition, genes involved in the regulaton of H3K27 methylation were also affected. Interestingly, connective tissue growth factor (CTGF), which is involved in TGF-b, BMP and Wnt signaling, was upregulated in both stromal and LSK cells in the first day of co-culture. To study a possible extrinsic role of CTGF as a stromal mediator, we co-cultured siCTGF knockdown stromal cells with wild-type LSK cells. Since self-renewal requires cell division, we focused on cell cycle regulation of LSK cells. We found that knockdown of CTGF in stromal cells downregulates CTGF in LSK cells. In addition, knockdown of stromal CTGF downregulated Ccnd1, Cdk2, Cdkn1a (p21), Ep300 and Fos. On the other hand, decreased CTGF in stromal cells upregulates Cdkn1b (p27) and phosphorylation of Smad2/3. These results show that stromal CTGF regulates the cell cycle of LSK cells. On a functional level, we found that decreased stromal CTGF results in an increased production of MPP and myeloid colony-forming cells in 1-week co-cultures. We will present data showing whether and how a decrease in CTGF in stromal cells affects the maintenance of transplantable HSC. In summary, our current results indicate that reduced expression of CTGF in stromal cells regulates mediators of cell cycle and Smad2/3-mediated signaling in LSK cells, resulting in an increased production of myeloid progenitors. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cell-cycle coupled expression minimizes random fluctuations in gene product levels

2016 ◽  
Author(s):  
Mohammad Soltani ◽  
Abhyudai Singh
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Regulatory Proteins ◽  
Daughter Cells ◽  
Stochastic Component ◽  
Stochastic Expression ◽  
A Cell ◽  
Intrinsic Stochasticity ◽  
Random Fluctuations ◽  
Cell To Cell Variability

AbstractExpression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyze a model, where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulas quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulas reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division minimizes noise from bursty expression for a fixed mean protein level. In contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression.

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 Mutual antagonism between Hippo signaling and cyclin E drives intracellular pattern formation

2020 ◽  
Vol 219 (9) ◽  
Author(s):  
Yu-Yang Jiang ◽  
Wolfgang Maier ◽  
Uzoamaka N. Chukka ◽  
Michael Choromanski ◽  
Chinkyu Lee ◽  
...  
Keyword(s):  
Cell Division ◽  
Pattern Formation ◽  
Tandem Duplication ◽  
Tetrahymena Thermophila ◽  
Cyclin E ◽  
Parental Cell ◽  
Hippo Signaling ◽  
Daughter Cells ◽  
Mutual Antagonism ◽  
A Cell

Not much is known about how organelles organize into patterns. In ciliates, the cortical pattern is propagated during “tandem duplication,” a cell division that remodels the parental cell into two daughter cells. A key step is the formation of the division boundary along the cell’s equator. In Tetrahymena thermophila, the cdaA alleles prevent the formation of the division boundary. We find that the CDAA gene encodes a cyclin E that accumulates in the posterior cell half, concurrently with accumulation of CdaI, a Hippo/Mst kinase, in the anterior cell half. The division boundary forms between the margins of expression of CdaI and CdaA, which exclude each other from their own cortical domains. The activities of CdaA and CdaI must be balanced to initiate the division boundary and to position it along the cell’s equator. CdaA and CdaI cooperate to position organelles near the new cell ends. Our data point to an intracellular positioning mechanism involving antagonistic Hippo signaling and cyclin E.

scholarly journals Growth and single cell kinetics of the loricate choanoflagellate Diaphanoeca grandis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Niels Thomas Eriksen ◽  
Jakob Tophøj ◽  
Rasmus Dam Wollenberg ◽  
Teis Esben Sondergaard ◽  
Peter Funch ◽  
...  
Keyword(s):  
Cell Division ◽  
Single Cell ◽  
Life Histories ◽  
Daughter Cell ◽  
Cell Kinetics ◽  
Cell Formation ◽  
Daughter Cells ◽  
History Of ◽  
A Cell ◽  
Multiple Cell

Abstract Choanoflagellates are common members of planktonic communities. Some have complex life histories that involve transitions between multiple cell stages. We have grown the loricate choanoflagellate Diaphanoeca grandis on the bacterium Pantoea sp. and integrated kinetic observations at the culture level and at the single cell level. The life history of D. grandis includes a cell division cycle with a number of recognisable cell stages. Mature, loricate D. grandis were immobile and settled on the bottom substratum. Daughter cells were ejected from the lorica 30 min. after cell division, became motile and glided on the bottom substratum until they assembled a lorica. Single cell kinetics could explain overall growth kinetics in D. grandis cultures. The specific growth rate was 0.72 day−1 during exponential growth while mature D. grandis produced daughter cells at a rate of 0.9 day−1. Daughter cells took about 1.2 h to mature. D. grandis was able to abandon and replace its lorica, an event that delayed daughter cell formation by more than 2 days. The frequency of daughter cell formation varied considerably among individuals and single cell kinetics demonstrated an extensive degree of heterogeneity in D. grandis cultures, also when growth appeared to be balanced.

scholarly journals DNA replication and mitotic entry: A brake model for cell cycle progression

2019 ◽  
Vol 218 (12) ◽  
pp. 3892-3902 ◽  
Author(s):  
Bennie Lemmens ◽  
Arne Lindqvist
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Cycle Model ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Core Function ◽  
A Cell

The core function of the cell cycle is to duplicate the genome and divide the duplicated DNA into two daughter cells. These processes need to be carefully coordinated, as cell division before DNA replication is complete leads to genome instability and cell death. Recent observations show that DNA replication, far from being only a consequence of cell cycle progression, plays a key role in coordinating cell cycle activities. DNA replication, through checkpoint kinase signaling, restricts the activity of cyclin-dependent kinases (CDKs) that promote cell division. The S/G2 transition is therefore emerging as a crucial regulatory step to determine the timing of mitosis. Here we discuss recent observations that redefine the coupling between DNA replication and cell division and incorporate these insights into an updated cell cycle model for human cells. We propose a cell cycle model based on a single trigger and sequential releases of three molecular brakes that determine the kinetics of CDK activation.

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