scholarly journals The Impact of Elastic Deformations of the Extracellular Matrix on Cell Migration

2020 ◽  
Vol 82 (4) ◽  
Author(s):  
A. A. Malik ◽  
B. Wennberg ◽  
P. Gerlee
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Human Cancer ◽  
Matrix Stiffness ◽  
Human Cancer Cells ◽  
Adhesion Sites ◽  
The Matrix ◽  
A Cell ◽  
Necessary And Sufficient ◽  
The Impact

Abstract The mechanical properties of the extracellular matrix, in particular its stiffness, are known to impact cell migration. In this paper, we develop a mathematical model of a single cell migrating on an elastic matrix, which accounts for the deformation of the matrix induced by forces exerted by the cell, and investigate how the stiffness impacts the direction and speed of migration. We model a cell in 1D as a nucleus connected to a number of adhesion sites through elastic springs. The cell migrates by randomly updating the position of its adhesion sites. We start by investigating the case where the cell springs are constant, and then go on to assuming that they depend on the matrix stiffness, on matrices of both uniform stiffness as well as those with a stiffness gradient. We find that the assumption that cell springs depend on the substrate stiffness is necessary and sufficient for an efficient durotactic response. We compare simulations to recent experimental observations of human cancer cells exhibiting durotaxis, which show good qualitative agreement.

scholarly journals An Overview of Matrix Rhythm Concept and Efficacy of Matrix Rhythm Therapy in Pathological Conditions

2019 ◽  
pp. 25-30
Author(s):  
Sonali Shrivastava ◽  
arif K. S.
Keyword(s):  
Extracellular Matrix ◽  
Muscle Tension ◽  
Frozen Shoulder ◽  
Cellular Level ◽  
Pulsation Frequency ◽  
Frequency Range ◽  
Pathological Conditions ◽  
The Matrix ◽  
A Cell ◽  
Living Process

Matrix Rhythm concept was introduced in1996 based upon the concept that every intervention on a cell whether preventive, curative, regenerative or also destructive works primarily via the cells environment, that is via the extracellular matrix. Muscle cells pulsate in the frequency range of 8-12 Hertz. Muscle pulsation frequency which lie outside 8-12 Hertz range correlate positively with pains, muscle tension and other health problems. Changed muscle elasticity and plasticity are linked to variations in pulsation frequency and in logistics the living process on the cellular level. In this paper we have reviewed the Matrix Rhythm Concept and practices of Matrix Rhythm Therapy in treating various pathological conditions. The application of matrix rhythm therapy in various conditions like frozen shoulder, post burn complications etc. are detailed.

scholarly journals The Anticancer Drug 3-Bromopyruvate Induces DNA Damage Potentially Through Reactive Oxygen Species in Yeast and in Human Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1161 ◽  
Author(s):  
Magdalena Cal ◽  
Irwin Matyjaszczyk ◽  
Ireneusz Litwin ◽  
Daria Augustyniak ◽  
Rafał Ogórek ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Cancer Cells ◽  
Human Cancer ◽  
Reactive Oxygen ◽  
Atp Depletion ◽  
Mitochondrial Enzymes ◽  
Oxygen Species ◽  
Human Cancer Cells ◽  
The Impact

3-bromopyruvate (3-BP) is a small molecule with anticancer and antimicrobial activities. 3-BP is taken up selectively by cancer cells’ mono-carboxylate transporters (MCTs), which are highly overexpressed by many cancers. When 3-BP enters cancer cells it inactivates several glycolytic and mitochondrial enzymes, leading to ATP depletion and the generation of reactive oxygen species. While mechanisms of 3-BP uptake and its influence on cell metabolism are well understood, the impact of 3-BP at certain concentrations on DNA integrity has never been investigated in detail. Here we have collected several lines of evidence suggesting that 3-BP induces DNA damage probably as a result of ROS generation, in both yeast and human cancer cells, when its concentration is sufficiently low and most cells are still viable. We also demonstrate that in yeast 3-BP treatment leads to generation of DNA double-strand breaks only in S-phase of the cell cycle, possibly as a result of oxidative DNA damage. This leads to DNA damage, checkpoint activation and focal accumulation of the DNA response proteins. Interestingly, in human cancer cells exposure to 3-BP also induces DNA breaks that trigger H2A.X phosphorylation. Our current data shed new light on the mechanisms by which a sufficiently low concentration of 3-BP can induce cytotoxicity at the DNA level, a finding that might be important for the future design of anticancer therapies.

scholarly journals T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Damien Garbett ◽  
Anjali Bisaria ◽  
Changsong Yang ◽  
Dannielle G. McCarthy ◽  
Arnold Hayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Actin Filaments ◽  
Myosin Ii ◽  
Adhesion Sites ◽  
Membrane Protrusions ◽  
And Migration ◽  
Muscle Myosin ◽  
Migrating Cells

Abstract Migrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.

scholarly journals Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors

2020 ◽  
Vol 295 (44) ◽  
pp. 15112-15133
Author(s):  
Elizabeth T. Abshire ◽  
Kelsey L. Hughes ◽  
Rucheng Diao ◽  
Sarah Pearce ◽  
Shreekara Gopalakrishna ◽  
...  
Keyword(s):  
Intracellular Localization ◽  
Tissue Type ◽  
Mrna Levels ◽  
Cellular Functions ◽  
Mitochondrial Functions ◽  
A Cell ◽  
Necessary And Sufficient ◽  
The Impact ◽  
Expression Processing ◽  
In Cells

Nocturnin (NOCT) is a eukaryotic enzyme that belongs to a superfamily of exoribonucleases, endonucleases, and phosphatases. In this study, we analyze the expression, processing, localization, and cellular functions of human NOCT. We find that NOCT protein is differentially expressed and processed in a cell and tissue type–specific manner to control its localization to the cytoplasm or mitochondrial exterior or interior. The N terminus of NOCT is necessary and sufficient to confer import and processing in the mitochondria. We measured the impact of cytoplasmic NOCT on the transcriptome and observed that it affects mRNA levels of hundreds of genes that are significantly enriched in osteoblast, neuronal, and mitochondrial functions. Recent biochemical data indicate that NOCT dephosphorylates NADP(H) metabolites, and thus we measured the effect of NOCT on these cofactors in cells. We find that NOCT increases NAD(H) and decreases NADP(H) levels in a manner dependent on its intracellular localization. Collectively, our data indicate that NOCT can regulate levels of both mRNAs and NADP(H) cofactors in a manner specified by its location in cells.

Enhancement of antiproliferative activity by phototautomerization of anthrylphenols

2015 ◽  
Vol 14 (6) ◽  
pp. 1082-1092 ◽  
Author(s):  
Marijeta Kralj ◽  
Lidija Uzelac ◽  
Yu-Hsuan Wang ◽  
Peter Wan ◽  
Martina Tireli ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Quinone Methide ◽  
Cellular Proteins ◽  
Human Cancer Cells ◽  
The Impact

9-(2-Hydroxyphenyl)anthracene (1) moderately inhibited the proliferation of human cancer cells, but irradiation considerably enhanced the effect due to the formation of quinone methide. The effect is not only due to the damage of DNA, but also due to the impact on the cellular proteins.

scholarly journals Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration

2021 ◽  
Author(s):  
Themistoklis Zisis ◽  
David B. Brückner ◽  
Tom Brandstätter ◽  
Joseph d'Alessandro ◽  
Angelika M. Vollmar ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Cell Dispersion ◽  
Intercellular Contacts ◽  
Quantitative Understanding ◽  
Average Spreading ◽  
Colony Spreading

Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-Cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). Inhibition of E- and N-Cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.

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