Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells

Abstract Recent studies have revealed that global extrinsic noise arising from stochasticity in the intracellular biochemical environment plays a critical role in heterogeneous cell physiologies. However, it remains largely unclear how such extrinsic noise dynamically influences downstream reactions...

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Main Authors: Jiegen Wu, Xu Han, Haotian Zhai, Tingyu Yang, Yihan Lin
Format: Article
Language:English
Published: Springer Nature 2020-05-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20199335
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author Jiegen Wu
Xu Han
Haotian Zhai
Tingyu Yang
Yihan Lin
author_facet Jiegen Wu
Xu Han
Haotian Zhai
Tingyu Yang
Yihan Lin
author_sort Jiegen Wu
collection DOAJ
description Abstract Recent studies have revealed that global extrinsic noise arising from stochasticity in the intracellular biochemical environment plays a critical role in heterogeneous cell physiologies. However, it remains largely unclear how such extrinsic noise dynamically influences downstream reactions and whether it could be neutralized by cellular reactions. Here, using fluorescent protein (FP) maturation as a model biochemical reaction, we explored how cellular reactions might combat global extrinsic noise in mammalian cells. We developed a novel single‐cell assay to systematically quantify the maturation rate and the associated noise for over a dozen FPs. By exploiting the variation in the maturation rate for different FPs, we inferred that global extrinsic noise could be temporally filtered by maturation reactions, and as a result, the noise levels for slow‐maturing FPs are lower compared to fast‐maturing FPs. This mechanism is validated by directly perturbing the maturation rates of specific FPs and measuring the resulting noise levels. Together, our results revealed a potentially general principle governing extrinsic noise propagation, where timescale separation allows cellular reactions to cope with dynamic global extrinsic noise.
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spelling doaj.art-8c75f3c3af844a4c87fa587e580dba832024-03-02T23:49:15ZengSpringer NatureMolecular Systems Biology1744-42922020-05-01165n/an/a10.15252/msb.20199335Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cellsJiegen Wu0Xu Han1Haotian Zhai2Tingyu Yang3Yihan Lin4Center for Quantitative Biology and Peking‐Tsinghua Joint Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing ChinaCenter for Quantitative Biology and Peking‐Tsinghua Joint Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing ChinaCenter for Quantitative Biology and Peking‐Tsinghua Joint Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing ChinaCenter for Quantitative Biology and Peking‐Tsinghua Joint Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing ChinaCenter for Quantitative Biology and Peking‐Tsinghua Joint Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing ChinaAbstract Recent studies have revealed that global extrinsic noise arising from stochasticity in the intracellular biochemical environment plays a critical role in heterogeneous cell physiologies. However, it remains largely unclear how such extrinsic noise dynamically influences downstream reactions and whether it could be neutralized by cellular reactions. Here, using fluorescent protein (FP) maturation as a model biochemical reaction, we explored how cellular reactions might combat global extrinsic noise in mammalian cells. We developed a novel single‐cell assay to systematically quantify the maturation rate and the associated noise for over a dozen FPs. By exploiting the variation in the maturation rate for different FPs, we inferred that global extrinsic noise could be temporally filtered by maturation reactions, and as a result, the noise levels for slow‐maturing FPs are lower compared to fast‐maturing FPs. This mechanism is validated by directly perturbing the maturation rates of specific FPs and measuring the resulting noise levels. Together, our results revealed a potentially general principle governing extrinsic noise propagation, where timescale separation allows cellular reactions to cope with dynamic global extrinsic noise.https://doi.org/10.15252/msb.20199335biological noisechromophore maturationfluorescent proteinglobal extrinsic noise
spellingShingle Jiegen Wu
Xu Han
Haotian Zhai
Tingyu Yang
Yihan Lin
Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
Molecular Systems Biology
biological noise
chromophore maturation
fluorescent protein
global extrinsic noise
title Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
title_full Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
title_fullStr Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
title_full_unstemmed Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
title_short Evidence for rate‐dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
title_sort evidence for rate dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells
topic biological noise
chromophore maturation
fluorescent protein
global extrinsic noise
url https://doi.org/10.15252/msb.20199335
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