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Effect of cyto/chemokine degradation in effective intercellular communication distances.

ABSTRACT: Many complex biological processes such as cell differentiation, cell proliferation, and cell motility are governed by cell signaling. This mode of intercellular communication is of paramount importance for tissue function and ultimately for entire organism. In intercellular communication cells secrete signaling molecules such as cyto/chemokines which diffuse through the surrounding medium and eventually bind to receptors on other cells whereby the signal transduction is completed. An accurate estimation of the effective communication distances and the time scale on which signaling takes place are important for the interpretation of cell and organ physiology and ultimately in the effective and efficient chemotactically driven tissue engineering. The present study uses a solitary cell model incorporating degradation of secreted molecules to estimate the effective communication distances and the time scale on which signaling takes place. We demonstrate through our model that in presence of degradation the effective communication distances are significantly reduced.

SUBMITTER: Gupta VK

PROVIDER: S-EPMC5473664 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Effect of cyto/chemokine degradation in effective intercellular communication distances.

Gupta V K VK

Physica A 20161111

Many complex biological processes such as cell differentiation, cell proliferation, and cell motility are governed by cell signaling. This mode of intercellular communication is of paramount importance for tissue function and ultimately for entire organism. In intercellular communication cells secrete signaling molecules such as cyto/chemokines which diffuse through the surrounding medium and eventually bind to receptors on other cells whereby the signal transduction is completed. An accurate es ...[more]

PMID: 28630529

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Project description:Robust self-sustained oscillations are a ubiquitous characteristic of circadian rhythms. These include Drosophila locomotor activity rhythms, which persist for weeks in constant darkness (DD). Yet the molecular oscillations that underlie circadian rhythms damp rapidly in many Drosophila tissues. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms that underlie the differences between damped and self-sustaining oscillations remain largely unknown. A small cluster of neurons in adult Drosophila brain, the ventral lateral neurons (LN(v)s), is essential for self-sustained behavioral rhythms and has been proposed to be the primary pacemaker for locomotor activity rhythms. With an LN(v)-specific driver, we restricted functional clocks to these neurons and showed that they are not sufficient to drive circadian locomotor activity rhythms. Also contrary to expectation, we found that all brain clock neurons manifest robust circadian oscillations of timeless and cryptochrome RNA for many days in DD. This persistent molecular rhythm requires pigment-dispersing factor (PDF), an LN(v)-specific neuropeptide, because the molecular oscillations are gradually lost when Pdf(01) mutant flies are exposed to free-running conditions. This observation precisely parallels the previously reported effect on behavioral rhythms of the Pdf(01) mutant. PDF is likely to affect some clock neurons directly, since the peptide appears to bind to the surface of many clock neurons, including the LN(v)s themselves. We showed that the brain circadian clock in Drosophila is clearly distinguishable from the eyes and other rapidly damping peripheral tissues, as it sustains robust molecular oscillations in DD. At the same time, different clock neurons are likely to work cooperatively within the brain, because the LN(v)s alone are insufficient to support the circadian program. Based on the damping results with Pdf(01) mutant flies, we propose that LN(v)s, and specifically the PDF neuropeptide that it synthesizes, are important in coordinating a circadian cellular network within the brain. The cooperative function of this network appears to be necessary for maintaining robust molecular oscillations in DD and is the basis of sustained circadian locomotor activity rhythms.

Project description:Cell-to-cell communication is a fundamental process for development and maintenance of multicellular organisms. Diverse mechanisms for the exchange of molecular information between cells have been documented, such as the exchange of membrane fragments (trogocytosis), formation of tunneling nanotubes (TNTs) and release of microvesicles (MVs). In this study we assign to Fas signalling a pivotal role for intercellular communication in CD4+ T cells. Binding of membrane-bound FasL to Fas expressing target cells triggers a well-characterized pro-apoptotic signalling cascade. However, our results, pairing up flow cytometric studies with confocal microscopy data, highlight a new social dimension for Fas/FasL interactions between CD4+ T cells. Indeed, FasL enhances the formation of cell conjugates (8 fold of increase) in an early time-frame of stimulation (30 min), and this phenomenon appears to be a crucial step to prime intercellular communication. Our findings show that this communication mainly proceeds along a cytosolic material exchange (ratio of exchange >10, calculated as ratio of stimulated cells signal divided by that recorded in control cells) via TNTs and MVs release. In particular, inhibition of TNTs genesis by pharmacological agents (Latruculin A and Nocodazole) markedly reduced this exchange (inhibition percentage: >40% and >50% respectively), suggesting a key role for TNTs in CD4+ T cells communication. Although MVs are present in supernatants from PHA-activated T cells, Fas treatment also leads to a significant increase in the amount of released MVs. In fact, the co-culture performed between MVs and untreated cells highlights a higher presence of MVs in the medium (1.4 fold of increase) and a significant MVs uptake (6 fold of increase) by untreated T lymphocytes. We conclude that Fas signalling induces intercellular communication in CD4+ T cells by different mechanisms that seem to start concomitantly with the main pathway (programmed cell death) promoted by FasL.

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Effect of cyto/chemokine degradation in effective intercellular communication distances.

Publications

Effect of cyto/chemokine degradation in effective intercellular communication distances.

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