Phase separation provides a mechanism to reduce noise in cells

Science ◽  
2020 ◽  
Vol 367 (6476) ◽  
pp. 464-468 ◽  
Author(s):  
A. Klosin ◽  
F. Oltsch ◽  
T. Harmon ◽  
A. Honigmann ◽  
F. Jülicher ◽  
...  
Keyword(s):  
Signal Processing ◽  
Phase Separation ◽  
Physical Model ◽  
Mammalian Cells ◽  
Protein Concentration ◽  
Liquid Droplets ◽  
Potential Mechanism ◽  
Biological Signal Processing ◽  
Cellular Control ◽  
And Control

Expression of proteins inside cells is noisy, causing variability in protein concentration among identical cells. A central problem in cellular control is how cells cope with this inherent noise. Compartmentalization of proteins through phase separation has been suggested as a potential mechanism to reduce noise, but systematic studies to support this idea have been missing. In this study, we used a physical model that links noise in protein concentration to theory of phase separation to show that liquid droplets can effectively reduce noise. We provide experimental support for noise reduction by phase separation using engineered proteins that form liquid-like compartments in mammalian cells. Thus, phase separation can play an important role in biological signal processing and control.

scholarly journals Phase separation provides a mechanism to reduce noise in cells

2019 ◽  
Author(s):  
Florian Oltsch ◽  
Adam Klosin ◽  
Frank Julicher ◽  
Anthony A. Hyman ◽  
Christoph Zechner
Keyword(s):  
Gene Expression ◽  
Phase Separation ◽  
Mammalian Cells ◽  
Biological Information ◽  
Liquid Droplets ◽  
Gene Expression Noise ◽  
Noise In Gene Expression ◽  
Biological Information Processing ◽  
Cellular Control

A central problem in cellular control is how cells cope with the inherent noise in gene expression. Although transcriptional and posttranscriptional feedback mechanisms can suppress noise, they are often slow, and cannot explain how cells buffer acute fluctuations. Here, by using a physical model that links fluctuations in protein concentration to the theory of phase separation, we show that liquid droplets can act as fast and effective buffers for gene expression noise. We confirm our theory experimentally using an engineered phase separating protein that forms liquid-like compartments in mammalian cells. These data suggest a novel role of phase separation in biological information processing.

scholarly journals Cheetah: a computational toolkit for cybergenetic control

2020 ◽  
Author(s):  
Elisa Pedone ◽  
Irene de Cesare ◽  
Criseida Zamora ◽  
David Haener ◽  
Lorena Postiglione ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Control Engineering ◽  
Segmentation Accuracy ◽  
Mammalian Cell Growth ◽  
Cell Monitoring ◽  
Microscopy Analysis ◽  
Cellular Phenotypes ◽  
Cellular Control ◽  
And Control ◽  
Core Capabilities

AbstractAdvances in microscopy, microfluidics and optogenetics enable single-cell monitoring and environmental regulation and offer the means to control cellular phenotypes. The development of such systems is challenging and often results in bespoke setups that hinder reproducibility. To address this, we introduce Cheetah – a flexible computational toolkit that simplifies the integration of real-time microscopy analysis with algorithms for cellular control. Central to the platform is an image segmentation system based on the versatile U-Net convolutional neural network. This is supplemented with functionality to robustly count, characterise and control cells over time. We demonstrate Cheetah’s core capabilities by analysing long-term bacterial and mammalian cell growth and by dynamically controlling protein expression in mammalian cells. In all cases, Cheetah’s segmentation accuracy exceeds that of a commonly used thresholding-based method, allowing for more accurate control signals to be generated. Availability of this easy-to-use platform will make control engineering techniques more accessible and offer new ways to probe and manipulate living cells.

scholarly journals Biological Signal Processing with a Genetic Toggle Switch

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68345 ◽  
Author(s):  
Patrick Hillenbrand ◽  
Georg Fritz ◽  
Ulrich Gerland
Keyword(s):  
Signal Processing ◽  
Toggle Switch ◽  
Biological Signal ◽  
Biological Signal Processing

scholarly journals Multivalent proteins rapidly and reversibly phase-separate upon osmotic cell volume change

2019 ◽  
Author(s):  
Ameya P. Jalihal ◽  
Sethuramasundaram Pitchiaya ◽  
Lanbo Xiao ◽  
Pushpinder Bawa ◽  
Xia Jiang ◽  
...  
Keyword(s):  
Phase Separation ◽  
Cell Volume ◽  
Volume Change ◽  
Mammalian Cells ◽  
Internal State ◽  
Transcription Termination ◽  
Cell Types ◽  
List Type ◽  
Molecular Crowding ◽  
Minimal Impact

SUMMARYProcessing bodies (PBs) and stress granules (SGs) are prominent examples of sub-cellular, membrane-less compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ∼10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ∼100 s) with minimal impact on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Together, our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration that adapts the cell to volume change.GRAPHICAL ABSTRACTIN BRIEFCells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.HIGHLIGHTSDCP1A undergoes rapid and reversible hyperosmotic phase separation (HOPS)HOPS of DCP1A depends on its trimerization domainSelf-interacting multivalent proteins (valency ≥ 2) undergo HOPSHOPS of CPSF6 explains transcription termination defects during osmotic stress

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