Universal structures for adaptation in biochemical reaction networks

Araujo, Robyn P.; Liotta, Lance A.

doi:10.1038/s41467-023-38011-9

Cited by 9 publications

(25 citation statements)

References 44 publications

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“…This can be clearly seen in the design of enzymatic oscillators, which almost exclusively involve delayed negative feedback loops, although more complex motifs may be involved as well . More recently, researchers have shown how different large network topologies can lead to the same effective network motifs capable of, for example, homeostasis and how descriptions of larger networks can be reduced to smaller functional motifs . Network motifs can be used as a starting point for the design of specific behavior, inspired by either behavior shown in already existing ERNs , or recreating network motifs not found in ERNs but in other types of networks.…”

Section: Structural Principles Of Enzymatic Networkmentioning

confidence: 99%

Exploring Emergent Properties in Enzymatic Reaction Networks: Design and Control of Dynamic Functional Systems

Ghosh,

Baltussen,

Ivanov

et al. 2024

Chem. Rev.

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The intricate and complex features of enzymatic reaction networks (ERNs) play a key role in the emergence and sustenance of life. Constructing such networks in vitro enables stepwise build up in complexity and introduces the opportunity to control enzymatic activity using physicochemical stimuli. Rational design and modulation of network motifs enable the engineering of artificial systems with emergent functionalities. Such functional systems are useful for a variety of reasons such as creating new-to-nature dynamic materials, producing value-added chemicals, constructing metabolic modules for synthetic cells, and even enabling molecular computation. In this review, we offer insights into the chemical characteristics of ERNs while also delving into their potential applications and associated challenges.

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Section: Structural Principles Of Enzymatic Networkmentioning

confidence: 99%

Exploring Emergent Properties in Enzymatic Reaction Networks: Design and Control of Dynamic Functional Systems

Ghosh,

Baltussen,

Ivanov

et al. 2024

Chem. Rev.

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“…For any such CRN graph structure, a key integer invariant known as the deficiency of the CRN may be computed, providing a quantitative measure of the linear independence of the CRN reactions given their distribution into linkage classes (Feinberg, 2019;Araujo and Liotta, 2023b).…”

Section: − − →∅mentioning

confidence: 99%

“…In the context of RPA, such a decomposition into independent subnetworks allows us to distinguish the network reactions that contribute to the network's RPA capacity from reactions that play no role in the RPA capacity of the CRN (Araujo and Liotta, 2023b). Subnetworks are algebraically independent when their individual ranks sum to the rank of the parent network (Feinberg, 2019).…”

Section: Rpa In Cellular Cholesterolmentioning

confidence: 99%

“…RPA is a biological network property whereby one or more molecular concentrations within the network are maintained at a particular fixed 'setpoint' at steady state, independently of specific network parameter choices (i.e., robustly), and in spite of altered inputs or disturbances to the system (Cannon, 1929;Kitano, 2007;Aoki et al, 2019;Ang et al, 2010;Ferrell, 2016;Araujo, 2021, 2023). The mathematical principles underpinning RPA in complex biological networks are now well understood, and we now have access to a universal description of RPA at both the macroscale of biochemical reaction networks Liotta, 2018, 2023a), and at the network microscale of individual intermolecular interactions and chemical reactions (Araujo and Liotta, 2023b). In particular, it is now known that all RPA-capable networks, no matter how large or complex, are decomposable into two distinct and welldefined subnetwork modules -Opposer modules and Balancer modules Liotta, 2018, 2023a).…”

Section: Introductionmentioning

confidence: 99%

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Robust Homeostasis of Cellular Cholesterol via Antithetic Integral Control

Scheepers

Araujo

2023

Preprint

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Although cholesterol is essential for cellular viability and proliferation, it is highly toxic in excess. The concentration of cellular cholesterol must therefore be maintained within tight tolerances and is thought to be subject to a stringent form of homeostasis known as Robust Perfect Adaptation (RPA). While much is known about the cellular signalling interactions involved in cholesterol regulation, the specific chemical reaction network structures that might be responsible for the robust homeostatic regulation of cellular cholesterol have been entirely unclear until now. In particular, the molecular mechanisms responsible for sensing excess whole-cell cholesterol levels have not been identified previously, and no mathematical models to date have been able to capture an integral control implementation that could impose RPA on cellular cholesterol. Here we provide a detailed mathematical description of cholesterol regulation pathways in terms of biochemical reactions, based on an extensive review of experimental and clinical literature. We are able to decompose the associated chemical reaction network structures into several independent subnetworks, one of which is responsible for conferring RPA on several intracellular forms of cholesterol. Remarkably, our analysis reveals that RPA in the cholesterol concentration in the endoplasmic reticulum (ER) is almost certainly due to a well-characterised control strategy known as antithetic integral control which, in this case, involves the high-affinity binding of a multi-molecular transcription factor complex with cholesterol molecules that are excluded from the ER membrane. Our model provides a detailed framework for exploring the necessary biochemical conditions for robust homeostatic control of essential and tightly regulated cellular molecules such as cholesterol.

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“…It has recently become possible to construct biochemical reaction systems with intrinsic plastic adaptation capabilities by rationally combining existing basic reaction mechanisms. − This capability is based on the versatility of biomolecules, such as proteins, and the structure and dynamics of biochemical reaction systems . The principles underlying the plastic adaptability of biochemical reaction systems to their environment represent a crucial issue in academic fields dealing with biochemical reaction systems beyond systems biology …”

Section: Introductionmentioning

confidence: 99%

DNA Reaction System That Acquires Classical Conditioning

Nakakuki,

Toyonari,

Aso

et al. 2024

ACS Synth. Biol.

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Biochemical reaction networks can exhibit plastic adaptation to alter their functions in response to environmental changes. This capability is derived from the structure and dynamics of the reaction networks and the functionality of the biomolecule. This plastic adaptation in biochemical reaction systems is essentially related to memory and learning capabilities, which have been studied in DNA computing applications for the past decade. However, designing DNA reaction systems with memory and learning capabilities using the dynamic properties of biochemical reactions remains challenging. In this study, we propose a basic DNA reaction system design that acquires classical conditioning, a phenomenon underlying memory and learning, as a typical learning task. Our design is based on a simple mechanism of five DNA strand displacement reactions and two degradative reactions. The proposed DNA circuit can acquire or lose a new function under specific conditions, depending on the input history formed by repetitive stimuli, by exploiting the dynamic properties of biochemical reactions induced by different input timings.

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Universal structures for adaptation in biochemical reaction networks

Cited by 9 publications

References 44 publications

Exploring Emergent Properties in Enzymatic Reaction Networks: Design and Control of Dynamic Functional Systems

Exploring Emergent Properties in Enzymatic Reaction Networks: Design and Control of Dynamic Functional Systems

Robust Homeostasis of Cellular Cholesterol via Antithetic Integral Control

DNA Reaction System That Acquires Classical Conditioning

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