Biophysical forces rewire cell metabolism to guide microtubule-dependent cell mechanics

2020 ◽  
Author(s):  
Sukriti Kapoor
Keyword(s):  
Cell Mechanics ◽  
Cell Metabolism ◽  
Biophysical Forces ◽  
Dependent Cell

scholarly journals Biophysical forces rewire cell metabolism to guide microtubule-dependent cell mechanics

2020 ◽  
Author(s):  
Stephanie Torrino ◽  
Stephane Audebert ◽  
Ilyes Belhadj ◽  
Caroline Lacoux ◽  
Sabrina Pisano ◽  
...  
Keyword(s):  
Cell Mechanics ◽  
Cell Metabolism ◽  
Glutamine Metabolism ◽  
Mechanical Loads ◽  
Cell Functions ◽  
Biophysical Forces ◽  
Dependent Cell ◽  
And Migration ◽  
External Forces ◽  
And Behavior

AbstractMechanical signals regulate cell shape and influence cell metabolism and behavior. Cells withstand external forces by adjusting the stiffness of its cytoskeleton. Microtubules (MTs) act as compression-bearing elements in response to mechanical cues. Therefore, MT dynamics affect cell mechanics. Yet, how mechanical loads control MT dynamics to adjust cell mechanics to its locally constrained environment has remained unclear. Here, we show that mechanical forces rewire glutamine metabolism to promote MT glutamylation and force cell mechanics, thereby modulating mechanodependent cell functions. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, depletion of the tubulin glutamylase TTLL4 or overexpression of tubulin mutants lacking glutamylation site(s) increased MT dynamics, cell compliance and contractility, and thereby impacted cell spreading, proliferation and migration. Together our results indicate that mechanical cues sustain cell mechanics through glutaminolysis-dependent MT glutamylation, linking cell metabolism to MT dynamics and cell mechanics. Furthermore, our results decipher part of the enigmatic tubulin code that coordinates the fine tunable properties of MT mechanics, allowing cells to adjust the stiffness of their cytoskeleton to the mechanical loads of their environment.

scholarly journals Revealing the nanoindentation response of a single cell using a 3D structural finite element model

2021 ◽  
Author(s):  
Wenjian Yang ◽  
Damien Lacroix ◽  
Lay Poh Tan ◽  
Jinju Chen
Keyword(s):  
Finite Element ◽  
Finite Element Model ◽  
Cell Mechanics ◽  
Cone Angle ◽  
Element Model ◽  
Homogeneous Material ◽  
Physiological Conditions ◽  
Dependent Cell ◽  
Core Shell Structure ◽  
Indenter Geometry

AbstractChanges in the apparent moduli of cells have been reported to correlate with cell abnormalities and disease. Indentation is commonly used to measure these moduli; however, there is evidence to suggest that the indentation protocol employed affects the measured moduli, which can affect our understanding of how physiological conditions regulate cell mechanics. Most studies treat the cell as a homogeneous material or a simple core–shell structure consisting of cytoplasm and a nucleus: both are far from the real structure of cells. To study indentation protocol-dependent cell mechanics, a finite element model of key intracellular components (cortex layer, cytoplasm, actin stress fibres, microtubules, and nucleus) has instead been developed. Results have shown that the apparent moduli obtained with conical indenters decreased with increasing cone angle; however, this change was less significant for spherical indenters of increasing radii. Furthermore, the interplay between indenter geometry and intracellular components has also been studied, which is useful for understanding structure-mechanics-function relationships of cells.

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1972 ◽  
Vol 69 (1) ◽  
pp. 165-173 ◽  
Author(s):  
H. Schmidt ◽  
I. Noack ◽  
K. D. Voigt
Keyword(s):  
Cell Proliferation ◽  
Cell Metabolism ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Ventral Prostate ◽  
Nucleic Acid Content ◽  
The Difference ◽  
Independent Effects ◽  
Sites Of Action ◽  
Peripheral Metabolism

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.

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