scholarly journals A metabolic reaction–diffusion model for PKCα translocation via PIP2 hydrolysis in an endothelial cell

2020 ◽  
Vol 477 (20) ◽  
pp. 4071-4084
Author(s):  
Toshihiro Sera ◽  
Shiro Higa ◽  
Yan Zeshu ◽  
Kyosuke Takahi ◽  
Satoshi Miyamoto ◽  
...  

Hydrolysis of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) at the cell membrane induces the release of inositol 1,4,5-trisphosphate (IP3) into the cytoplasm and diffusion of diacylglycerol (DAG) through the membrane, respectively. Release of IP3 subsequently increases Ca2+ levels in the cytoplasm, which results in activation of protein kinase C α (PKCα) by Ca2+ and DAG, and finally the translocation of PKCα from the cytoplasm to the membrane. In this study, we developed a metabolic reaction–diffusion framework to simulate PKCα translocation via PIP2 hydrolysis in an endothelial cell. A three-dimensional cell model, divided into membrane and cytoplasm domains, was reconstructed from confocal microscopy images. The associated metabolic reactions were divided into their corresponding domain; PIP2 hydrolysis at the membrane domain resulted in DAG diffusion at the membrane domain and IP3 release into the cytoplasm domain. In the cytoplasm domain, Ca2+ was released from the endoplasmic reticulum, and IP3, Ca2+, and PKCα diffused through the cytoplasm. PKCα bound Ca2+ at, and diffused through, the cytoplasm, and was finally activated by binding with DAG at the membrane. Using our model, we analyzed IP3 and DAG dynamics, Ca2+ waves, and PKCα translocation in response to a microscopic stimulus. We found a qualitative agreement between our simulation results and our experimental results obtained by live-cell imaging. Interestingly, our results suggest that PKCα translocation is dominated by DAG dynamics. This three-dimensional reaction–diffusion mathematical framework could be used to investigate the link between PKCα activation in a cell and cell function.

2006 ◽  
Vol 128 (1-2) ◽  
pp. 5-20 ◽  
Author(s):  
Vladimir Krstić ◽  
Željka Maglica ◽  
Hana Čipčić Paljetak ◽  
Boris Podobnik ◽  
Nenad Pavin

2020 ◽  
Author(s):  
Rinke J. van Tatenhove-Pel ◽  
Tomaž Rijavec ◽  
Aleš Lapanje ◽  
Iris van Swam ◽  
Emile Zwering ◽  
...  

AbstractMetabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 µm-sized metabolite producer, receiver and competitor cells in different spatial structures. We show that receivers cannot interact with producers ∼15 µm away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and created variants of the receiver cells’ import system, to show that within producer-receiver aggregates even low affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces the interaction distance to the low micrometer-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions.


2020 ◽  
Vol 117 (12) ◽  
pp. 6330-6338 ◽  
Author(s):  
Sven Flemming ◽  
Francesc Font ◽  
Sergio Alonso ◽  
Carsten Beta

Cytokinesis—the division of a cell into two daughter cells—is a key step in cell growth and proliferation. It typically occurs in synchrony with the cell cycle to ensure that a complete copy of the genetic information is passed on to the next generation of daughter cells. In animal cells, cytokinesis commonly relies on an actomyosin contractile ring that drives equatorial furrowing and separation into the two daughter cells. However, also contractile ring-independent forms of cell division are known that depend on substrate-mediated traction forces. Here, we report evidence of an as yet unknown type of contractile ring-independent cytokinesis that we termed wave-mediated cytofission. It is driven by self-organized cortical actin waves that travel across the ventral membrane of oversized, multinucleatedDictyostelium discoideumcells. Upon collision with the cell border, waves may initiate the formation of protrusions that elongate and eventually pinch off to form separate daughter cells. They are composed of a stable elongated wave segment that is enclosed by a cell membrane and moves in a highly persistent fashion. We rationalize our observations based on a noisy excitable reaction–diffusion model in combination with a dynamic phase field to account for the cell shape and demonstrate that daughter cells emerging from wave-mediated cytofission exhibit a well-controlled size.


2018 ◽  
Vol 36 (4) ◽  
pp. 439-469 ◽  
Author(s):  
Lucia Carichino ◽  
Sarah D Olson

AbstractChanges in calcium concentration along the sperm flagellum regulate sperm motility and hyperactivation, characterized by an increased flagellar bend amplitude and beat asymmetry, enabling the sperm to reach and penetrate the ovum (egg). The signalling pathways by which calcium increases within the flagellum are well established. However, the exact mechanisms of how calcium regulates flagellar bending are still under investigation. We extend our previous model of planar flagellar bending by developing a fluid-structure interaction model that couples the 3D motion of the flagellum in a viscous Newtonian fluid with the evolving calcium concentration. The flagellum is modelled as a Kirchhoff rod: an elastic rod with preferred curvature and twist. The calcium dynamics are represented as a 1D reaction–diffusion model on a moving domain, the flagellum. The two models are coupled assuming that the preferred curvature and twist of the sperm flagellum depend on the local calcium concentration. To investigate the effect of calcium on sperm motility, we compare model results of flagellar bend amplitude and swimming speed for three cases: planar, helical (spiral with equal amplitude in both directions), and quasi-planar (spiral with small amplitude in one direction). We observe that for the same parameters, the planar swimmer is faster and a turning motion is more clearly observed when calcium coupling is accounted for in the model. In the case of flagellar bending coupled to the calcium concentration, we observe emergent trajectories that can be characterized as a hypotrochoid for both quasi-planar and helical bending.


Author(s):  
C. Zmurchok ◽  
J. Collette ◽  
V. Rajagopal ◽  
W. R. Holmes

AbstractMigratory cells are known to adapt to environments that contain wide-ranging levels of chemoattractant. While biochemical models of adaptation have been previously proposed, here we discuss a different mechanism based on mechanosensing, where the interaction between biochemical signaling and cell tension facilitates adaptation. We describe and analyze a model of mechanochemical-based adaptation coupling a mechanics-based physical model of cell tension coupled with the wave-pinning reaction-diffusion model for Rac activity. Mathematical analysis of this model, simulations of a simplified 1D cell geometry, and 2D finite element simulations of deforming cells reveal that as a cell protrudes under the influence of high stimulation levels, tension mediated inhibition of GTPase signaling causes the cell to polarize even when initially over-stimulated. Specifically, tension mediated inhibition of GTPase activation, which has been experimentally observed in recent years, facilitates this adaptation by countering the high levels of environmental stimulation. These results demonstrate how tension related mechanosensing may provide an alternative (and potentially complementary) mechanism for cell adaptation.Statement of SignificanceMigratory cells such as human neutrophils encounter environments that contain wide-ranging levels of chemoattractant. In order to move, these cells must maintain an organized front-rear signaling polarity despite this wide variation in environmental stimuli. Past research has demonstrated a number of biochemical based mechanisms by which cells adapt to variable signal levels. Here we demonstrate that the interplay between Rho GTPase signaling and tension mediated feedbacks may provide an alternative mechanochemical mechanism for adaptation to high levels of signaling.


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