scholarly journals Intercellular communication induces glycolytic synchronization waves between individually oscillating cells

2021 ◽  
Vol 118 (6) ◽  
pp. e2010075118
Author(s):  
Martin Mojica-Benavides ◽  
David D. van Niekerk ◽  
Mite Mijalkov ◽  
Jacky L. Snoep ◽  
Bernhard Mehlig ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Mechanistic Model ◽  
Reaction Chamber ◽  
Microfluidic System ◽  
Flow Chamber ◽  
Cellular Heterogeneity ◽  
Yeast Cells ◽  
Peripheral Blood Flow ◽  
Synchronized Cells ◽  
Spatially Differentiated

Many organs have internal structures with spatially differentiated and sometimes temporally synchronized groups of cells. The mechanisms leading to such differentiation and coordination are not well understood. Here we design a diffusion-limited microfluidic system to mimic a multicellular organ structure with peripheral blood flow and test whether a group of individually oscillating yeast cells could form subpopulations of spatially differentiated and temporally synchronized cells. Upon substrate addition, the dynamic response at single-cell level shows glycolytic oscillations, leading to wave fronts traveling through the monolayered population and to synchronized communities at well-defined positions in the cell chamber. A detailed mechanistic model with the architectural structure of the flow chamber incorporated successfully predicts the spatial-temporal experimental data, and allows for a molecular understanding of the observed phenomena. The intricate interplay of intracellular biochemical reaction networks leading to the oscillations, combined with intercellular communication via metabolic intermediates and fluid dynamics of the reaction chamber, is responsible for the generation of the subpopulations of synchronized cells. This mechanism, as analyzed from the model simulations, is experimentally tested using different concentrations of cyanide stress solutions. The results are reproducible and stable, despite cellular heterogeneity, and the spontaneous community development is reminiscent of a zoned cell differentiation often observed in multicellular organs.

scholarly journals Design and Manufacturing of a Disposable, Cyclo-Olefin Copolymer, Microfluidic Device for a Biosensor †

Sensors ◽  
2019 ◽  
Vol 19 (5) ◽  
pp. 1178 ◽  
Author(s):  
Jorge Prada ◽  
Christina Cordes ◽  
Carsten Harms ◽  
Walter Lang
Keyword(s):  
Microfluidic Device ◽  
Heating Temperature ◽  
Low Cost ◽  
Reaction Chamber ◽  
Microfluidic System ◽  
Heating Process ◽  
Design And Manufacturing ◽  
On Chip ◽  
Working Parameters ◽  
Auto Fluorescence

This contribution outlines the design and manufacturing of a microfluidic device implemented as a biosensor for retrieval and detection of bacteria RNA. The device is fully made of Cyclo-Olefin Copolymer (COC), which features low auto-fluorescence, biocompatibility and manufacturability by hot-embossing. The RNA retrieval was carried on after bacteria heat-lysis by an on-chip micro-heater, whose function was characterized at different working parameters. Carbon resistive temperature sensors were tested, characterized and printed on the biochip sealing film to monitor the heating process. Off-chip and on-chip processed RNA were hybridized with capture probes on the reaction chamber surface and identification was achieved by detection of fluorescence tags. The application of the mentioned techniques and materials proved to allow the development of low-cost, disposable albeit multi-functional microfluidic system, performing heating, temperature sensing and chemical reaction processes in the same device. By proving its effectiveness, this device contributes a reference to show the integration potential of fully thermoplastic devices in biosensor systems.

scholarly journals Ageing and hygroscopicity variation of black carbon particles in Beijing measured by a quasi-atmospheric aerosol evolution study (QUALITY) chamber

2017 ◽  
Vol 17 (17) ◽  
pp. 10333-10348 ◽  
Author(s):  
Jianfei Peng ◽  
Min Hu ◽  
Song Guo ◽  
Zhuofei Du ◽  
Dongjie Shang ◽  
...  
Keyword(s):  
Black Carbon ◽  
Atmospheric Aerosol ◽  
Ambient Air ◽  
Reaction Chamber ◽  
Flow Chamber ◽  
Study Quality ◽  
Hygroscopic Growth ◽  
Coating Materials ◽  
Average Growth ◽  
Evolution Study

Abstract. Measurements of ageing and hygroscopicity variation of black carbon (BC) particles in Beijing were conducted using a 1.2 m3 quasi-atmospheric aerosol evolution study (QUALITY) chamber, which consisted of a bottom flow chamber through which ambient air was pulled continuously and an upper reaction chamber where ageing of BC particles occurred. Within the reaction chamber, transmission of the solar ultraviolet irradiation was approximately 50–60 %, wall loss of primary gaseous pollutants was negligible, and BC exhibited a half-lifetime of about 3–7 h. Typically, equilibrium for the primary gases, temperature and relative humidity between the reaction chamber and ambient air was established within 1 h. Rapid growth of BC particles occurred, with an average total growth of 77 ± 33 nm and average growth rate of 26 ± 11 nm h−1. Secondary organic aerosols (SOA) accounted for more than 90 % of the coating mass. The O ∕ C ratio of SOA was 0.5, lower than the ambient level. The hygroscopic growth factor of BC particles decreased slightly with an initial thin coating layer because of BC reconstruction, but subsequently increased to 1.06–1.08 upon further ageing. The κ (kappa) values for BC particles and coating materials were calculated as 0.035 and 0.040 at the subsaturation and supersaturation conditions, respectively, indicating low hygroscopicity of coated SOA on BC particles. Hence, our results indicate that initial photochemical ageing of BC particles leads to considerable modifications to morphology and optical properties but does not appreciably alter the particle hygroscopicity in Beijing.

Phosphofructokinase controls the acetaldehyde-induced phase shift in isolated yeast glycolytic oscillators

2019 ◽  
Vol 476 (2) ◽  
pp. 353-363
Author(s):  
David D. van Niekerk ◽  
Anna-Karin Gustavsson ◽  
Martin Mojica-Benavides ◽  
Caroline B. Adiels ◽  
Mattias Goksör ◽  
...  
Keyword(s):  
Phase Shift ◽  
Phase Response Curve ◽  
Mechanistic Model ◽  
Phase Response ◽  
Yeast Cells ◽  
Emergent Properties ◽  
Functional Coupling ◽  
External Signal ◽  
Oscillatory Systems ◽  
External Perturbations

Abstract The response of oscillatory systems to external perturbations is crucial for emergent properties such as synchronisation and phase locking and can be quantified in a phase response curve (PRC). In individual, oscillating yeast cells, we characterised experimentally the phase response of glycolytic oscillations for external acetaldehyde pulses and followed the transduction of the perturbation through the system. Subsequently, we analysed the control of the relevant system components in a detailed mechanistic model. The observed responses are interpreted in terms of the functional coupling and regulation in the reaction network. We find that our model quantitatively predicts the phase-dependent phase shift observed in the experimental data. The phase shift is in agreement with an adaptation leading to synchronisation with an external signal. Our model analysis establishes that phosphofructokinase plays a key role in the phase shift dynamics as shown in the PRC and adaptation time to external perturbations. Specific mechanism-based interventions, made possible through such analyses of detailed models, can improve upon standard trial and error methods, e.g. melatonin supplementation to overcome jet-lag, which are error-prone, specifically, since the effects are phase dependent and dose dependent. The models by Gustavsson and Goldbeter discussed in the text can be obtained from the JWS Online simulation database: (https://jjj.bio.vu.nl/models/gustavsson5 and https://jjj.bio.vu.nl/models/goldbeter1)

scholarly journals Metabolic cost of rapid adaptation of single yeast cells

2020 ◽  
Vol 117 (20) ◽  
pp. 10660-10666 ◽  
Author(s):  
Gabrielle Woronoff ◽  
Philippe Nghe ◽  
Jean Baudry ◽  
Laurent Boitard ◽  
Erez Braun ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Single Cells ◽  
A Priori ◽  
Metabolic Cost ◽  
Microfluidic System ◽  
Cellular Reprogramming ◽  
Yeast Cells ◽  
Rapid Adaptation ◽  
Metabolic Coupling ◽  
Induced Changes

Cells can rapidly adapt to changing environments through nongenetic processes; however, the metabolic cost of such adaptation has never been considered. Here we demonstrate metabolic coupling in a remarkable, rapid adaptation process (1 in 1,000 cells adapt per hour) by simultaneously measuring metabolism and division of thousands of individual Saccharomyces cerevisiae cells using a droplet microfluidic system: droplets containing single cells are immobilized in a two-dimensional (2D) array, with osmotically induced changes in droplet volume being used to measure cell metabolism, while simultaneously imaging the cells to measure division. Following a severe challenge, most cells, while not dividing, continue to metabolize, displaying a remarkably wide diversity of metabolic trajectories from which adaptation events can be anticipated. Adaptation requires a characteristic amount of energy, indicating that it is an active process. The demonstration that metabolic trajectories predict a priori adaptation events provides evidence of tight energetic coupling between metabolism and regulatory reorganization in adaptation. This process allows S. cerevisiae to adapt on a physiological timescale, but related phenomena may also be important in other processes, such as cellular differentiation, cellular reprogramming, and the emergence of drug resistance in cancer.

scholarly journals Design and Manufacturing of a Disposable, Cyclo-Olefin Copolymer, Microfluidic Biosensor

Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 810
Author(s):  
Jorge Prada ◽  
Christina Cordes ◽  
Carsten Harms ◽  
Walter Lang
Keyword(s):  
Heating Temperature ◽  
Low Cost ◽  
Reaction Chamber ◽  
Microfluidic System ◽  
Heating Process ◽  
Design And Manufacturing ◽  
Microfluidic Biosensor ◽  
On Chip ◽  
Auto Fluorescence ◽  
Reaction Processes

This contribution outlines the design and manufacturing of a biosensor for retrieval and detection of bacteria RNA. The device is fully made of Cyclo-Olefin Copolymer (COC), which features low auto-fluorescence, biocompatibility and manufacturability by hot-embossing. The RNA retrieval is carried on after bacteria heat-lysis by an on-chip micro-heater. Two additional carbon resistive temperature sensors printed on the biochip sealing film monitor the heating process. RNA is hybridized with capture probes on the reaction chamber surface and identification is achieved by detection of fluorescence tags. The application of the mentioned techniques and materials facilitates the development of low-cost, disposable albeit multi-functional microfluidic system, performing heating, temperature sensing and chemical reaction processes in the same device. By proving its effectiveness, this device contributes a reference to show the potential of fully thermoplastic devices as biosensors.

Entropy-based separation of yeast cells using a microfluidic system of conjoined spheres

2013 ◽  
Vol 114 (19) ◽  
pp. 194702 ◽  
Author(s):  
Kai-Jian Huang ◽  
S.-J. Qin ◽  
Zhong-Chen Bai ◽  
Xin Zhang ◽  
John D. Mai
Keyword(s):  
Microfluidic System ◽  
Yeast Cells

scholarly journals In S. cerevisiae hydroxycitric acid antagonizes chronological aging and apoptosis regardless of citrate lyase

APOPTOSIS ◽  
2020 ◽  
Vol 25 (9-10) ◽  
pp. 686-696
Author(s):  
Maurizio D. Baroni ◽  
Sonia Colombo ◽  
Olivier Libens ◽  
Rani Pallavi ◽  
Marco Giorgio ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Mechanistic Model ◽  
Yeast Cells ◽  
Signal Pathways ◽  
Atp Citrate Lyase ◽  
Chronological Aging ◽  
Hydroxycitric Acid ◽  
Age Related ◽  
Citrate Lyase ◽  
Bona Fide

Abstract Caloric restriction mimetics (CRMs) are promising molecules to prevent age-related diseases as they activate pathways driven by a true caloric restriction. Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy. Importantly, it can reduce inflammation and tumour development. In order to identify phenotypically relevant new HCA targets we have investigated HCA effects in Saccharomyces cerevisiae, where ACLY is lacking. Strikingly, the drug revealed a powerful anti-aging effect, another property proposed to mark bona fide CRMs. Chronological life span (CLS) extension but also resistance to acetic acid of HCA treated cells were associated to repression of cell apoptosis and necrosis. HCA also largely prevented cell deaths caused by a severe oxidative stress. The molecule could act widely by negatively modulating cell metabolism, similarly to citrate. Indeed, it inhibited both growth reactivation and the oxygen consumption rate of yeast cells in stationary phase. Genetic analyses on yeast CLS mutants indicated that part of the HCA effects can be sensed by Sch9 and Ras2, two conserved key regulators of nutritional and stress signal pathways of primary importance. Our data together with published biochemical analyses indicate that HCA may act with multiple mechanisms together with ACLY repression and allowed us to propose an integrated mechanistic model as a basis for future investigations.

scholarly journals High-throughput intracellular biopsy of microRNAs for dissecting the temporal dynamics of cellular heterogeneity

2020 ◽  
Vol 6 (24) ◽  
pp. eaba4971
Author(s):  
Zixun Wang ◽  
Lin Qi ◽  
Yang Yang ◽  
Mingxing Lu ◽  
Kai Xie ◽  
...  
Keyword(s):  
Rna Binding ◽  
Temporal Dynamics ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Single Copy ◽  
Reaction Chamber ◽  
Cellular Heterogeneity ◽  
Cell Subpopulations ◽  
Cellular Phenotypes

The capability to analyze small RNAs responsible for post-transcriptional regulation of genes expression is essential for characterizing cellular phenotypes. Here, we describe an intracellular biopsy technique (inCell-Biopsy) for fast, multiplexed, and highly sensitive profiling of microRNAs (miRNAs). The technique uses an array of diamond nanoneedles that are functionalized with size-dependent RNA binding proteins, working as “fishing rods” to directly pull miRNAs out of cytoplasm while keeping the cells alive, thus enabling quasi-single-cell miRNA analysis. Each nanoneedle works as a reaction chamber for parallel in situ amplification, visualization, and quantification of miRNAs as low as femtomolar, which is sufficient to detect miRNAs of a single-copy intracellular abundance with specificity to single-nucleotide variation. Using inCell-Biopsy, we analyze the temporal miRNA transcriptome over the differentiation of embryonic stem cells (ESCs). The combinatorial miRNA expression patterns derived by inCell-Biopsy identify emerging cell subpopulations differentiated from ESCs and reveal the dynamic evolution of cellular heterogeneity.

scholarly journals Metabolic Cost of Rapid Adaptation of Single Yeast Cells

2019 ◽  
Author(s):  
Gabrielle Woronoff ◽  
Philippe Nghe ◽  
Jean Baudry ◽  
Laurent Boitard ◽  
Erez Braun ◽  
...  
Keyword(s):  
A Priori ◽  
Metabolic Cost ◽  
Microfluidic System ◽  
Yeast Cells ◽  
Rapid Adaptation ◽  
Tight Coupling ◽  
Cell Level ◽  
Changing Environments ◽  
Regulatory Processes ◽  
Metabolic Coupling

AbstractCells can rapidly adapt to changing environments through non-genetic processes; however, the metabolic cost of such adaptation has never been considered. Here we demonstrate metabolic coupling in a remarkable, rapid adaptation process (10-3cells/hour) by simultaneously measuring metabolism and division of thousands of individual Saccharomyces cerevisiae cells using a droplet microfluidic system. Following a severe challenge, most cells, while not dividing, continue to metabolize, displaying a remarkably wide diversity of metabolic trajectories from which adaptation events can be anticipated. Adaptation requires the consumption of a characteristic amount of energy, indicating that it is an active process. The demonstration that metabolic trajectories predict a priori adaptation events provides the first evidence of tight energetic coupling between metabolism and regulatory reorganization in adaptation.One Sentence SummaryDemonstration of the tight coupling between metabolic activity and regulatory processes during rapid adaptation at the single-cell level.

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