Homeostatic artificial cells enable self-protection in prototissue spheroids

Chem, Год журнала: 2025, Номер unknown, С. 102409 - 102409

Опубликована: Фев. 1, 2025

The bigger pictureLiving cells form tissues with specialized functions that maintain homeostasis through feedback-regulated operations. In tissues, cellular communication and collective behavior are crucial for coordinating tasks ensuring overall functionality. Developing artificial (ACs) can be organized into prototissues to mimic these behaviors is a significant advancement toward creating functional AC systems. These systems essential understanding how design networks behaviors, deciphering life's fundamental principles, advancing biomedical applications. Here, we create AC-based prototissue spheroids stabilize their microenvironment against external pH threats using mechanism encoded within individual ACs. Like living communicate chemically collectively resist environmental challenges, paving the way more advanced in future.Highlights•Microfluidic production of reversible permeability•Homeostatic ACs modulate internal via chemo-structural feedback•Prototissues states threats•Inter-AC mixed counteracts threatsSummaryPrototissues made from aim replicate such as communication, behavior, homeostasis. Despite progress developing diverse types, building achieving effective well remain challenging. We introduce an intrinsic homeostatic control stable protect cargo fluctuations. contain pH-modulating enzymes pH-sensitive membrane, allowing self-regulation feedback. They adjust by importing substrates specific range self-regulate substrate influx. This enables them local pH, manage release, facilitate interactive spheroids. Our findings demonstrate potential synthetic tissue mimics, replicating protective communicative engineering applications.Graphical abstract

Язык: Английский

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Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12767 - 12767

Опубликована: Ноя. 27, 2024

The tryptophan-kynurenine (KYN) pathway has long been recognized for its essential role in generating metabolites that influence various physiological processes. Traditionally, these have categorized into distinct, often opposing groups, such as pro-oxidant versus antioxidant, excitotoxic/neurotoxic neuroprotective. This dichotomous framework shaped much of the research on conditions like neurodegenerative and neuropsychiatric disorders, well cancer, where metabolic imbalances are a key feature. effects significantly influenced by factors, including concentration particular cellular milieu which they generated. A molecule acts neuroprotective at low concentrations may exhibit neurotoxic elevated levels. oxidative equilibrium surrounding environment can alter function KYN from an antioxidant to pro-oxidant. narrative review offers comprehensive examination analysis contemporary understanding metabolites, emphasizing their multifaceted biological functions relevance numerous pathological underscores pressing necessity paradigm shift comprehension metabolism. Understanding context-dependent roles is vital novel therapies Alzheimer's disease, multiple sclerosis, cancer. Comprehensive modulation, balancing inflammatory signals enzyme regulation, promising avenues targeted, effective treatments.

Язык: Английский

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Bistable Functions and Signaling Motifs in Systems Chemistry: Taking the Next Step Toward Synthetic Cells

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

ConspectusA key challenge in modern chemistry research is to mimic life-like functions using simple molecular networks and the integration of such into first functional artificial cell. Central this endeavor development signaling elements that can regulate cell function time space by producing entities code with specific information induce downstream activity. Such motifs emerge nonequilibrium systems, exhibiting complex dynamic behavior like bistability, multistability, oscillations, chaos. However, de novo, bottom-up design systems remains challenging, primarily because kinetic characteristics energy aspects yielding bifurcation have not yet been globally defined. We herein review our recent work focuses on analysis peptide-based networks, propelled replication reactions bistable behavior. Furthermore, we rationalize discuss their exploitation implementation as variable homogeneous heterogeneous environments.The constitute reversible second-order autocatalysis positive feedback generate two distinct product distributions at steady state (SS), low-SS high-SS. Quantitative analyses reveal a phase transition from equilibration dynamics bistability takes place when system continuously fueled, reducing agent, keep it far equilibrium. In addition, an extensive set experimental, theoretical, simulation studies highlight defined parameter where operates.Analogous arrangement protein-based intracellular pathways, sequential concatenation synthetic used for signal processing media. The cascaded network output signals are switched erased or transduced manipulating order addition components, allowing reach "on demand" either pre-encoded also useful programming tool regulation nanoscale materials properties, bridging together Systems Chemistry Nanotechnology fields. cascade outputs serve input consecutive nanoparticle formation reaction growth processes, which–depending applied conditions–regulate various features (Au) shape assembly.Our enables production apparatus feature higher complexity than previously observed chemical networks. Future studies, briefly discussed end Account, will be directed more elaborate functionality, under flow conditions, oscillations. propose profound understanding principles facilitating replication-based related bear implications exploring origin protein functionality prior highly evolved replication–translation–transcription machinery. within future cells seems straightforward alternating states memory switch controlling division even communication among different cells. furthermore suggest introduced living biotechnology applications, switches temporal spatial manipulations.

Язык: Английский

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Evolution of complexity and the transition to biochemical life

Physical review. E, Год журнала: 2025, Номер 111(6)

Опубликована: Июнь 2, 2025

While modern physics and biology satisfactorily explain the passage from Big Bang to formation of Earth first cells present-day life, respectively, origins biochemical life still remain an open question. Since as we know it, requires extremely long genetic polymers, any answer question must how evolving system polymers ever-increasing length could come about on a planet that otherwise consisted only small molecular building blocks. In this work show that, under realistic constraints, abstract polymer model can exhibit dynamics such attractors in population space with higher average are also more probable. We generalize formalize notions for chemical reaction networks multiple attractors. The complexity species is defined minimum number reactions needed produce it set blocks, which turn used define measure attractor. A transition between considered be if attractor probability has complexity. environment where monomers readily available, complex. Thus, by criterion, our progressive evolution range thermodynamically plausible rate constants. criteria role autocatalysis obtaining them. Our provides basis searching prebiotically scenarios emerge yield populations even longer polymers. Additionally, existence features like history dependence endedness support view path chemistry was one gradual complexification rather than instantaneous origin life. Published American Physical Society 2025

Язык: Английский

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Kinetic Trapping of an Out‐of‐Equilibrium Dynamic Library of Imines by Changing Solvent

Chemistry - A European Journal, Год журнала: 2024, Номер 30(37)

Опубликована: Апрель 8, 2024

A well-behaved dynamic library composed of two imines and corresponding amines was subjected to the action an activated carboxylic acid (ACA), whose decarboxylation is known be base promoted, in different solvents, namely CD

Язык: Английский

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Forging out-of-equilibrium supramolecular gels

Nature Synthesis, Год журнала: 2024, Номер 3(12), С. 1481 - 1489

Опубликована: Сен. 6, 2024

Язык: Английский

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Advances in Bioinspired Artificial Systems Enabling Biomarker‐Driven Therapy

Chemistry - A European Journal, Год журнала: 2024, Номер 30(48)

Опубликована: Авг. 9, 2024

Abstract Bioinspired molecular engineering strategies have emerged as powerful tools that significantly enhance the development of novel therapeutics, improving efficacy, specificity, and safety in disease treatment. Recent advancements focused on identifying utilizing disease‐associated biomarkers to optimize drug activity address challenges inherent traditional such frequent administrations, poor patient adherence, increased risk adverse effects. In this review, we provide a comprehensive overview latest developments bioinspired artificial systems (BAS) use tailor therapeutic responses drugs presence disease‐specific biomarkers. We examine transition from open‐loop systems, which rely external cues, closed‐loop feedback capable autonomous self‐regulation response detail various BAS modalities designed achieve biomarker‐driven therapy, including activatable prodrug molecules, smart delivery platforms, cells, synthetic receptor‐based cell therapies, elucidating their operational principles practical vivo applications. Finally, discuss current future perspectives advancement BAS‐enabled technology envision ongoing toward more programmable customizable BAS‐based therapeutics will precision medicine.

Язык: Английский

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Supramolecular Systems Chemistry Based on the Interplay between Peptides and Porphyrins

ChemSystemsChem, Год журнала: 2024, Номер unknown

Опубликована: Окт. 23, 2024

Abstract The functions of living organisms are emergent from networks biomolecules. In this review, we discuss the creation synthetic life‐like systems based on interplay peptides and porphyrins in supramolecular chemical systems. particular, focus spatiotemporal control self‐assembly processes, which allows for development hierarchical structures biomimetic catalysis adaptive dynamics stimulus‐responsive structural transformations. Notably, when operating a nonequilibrium regime–characterized by kinetic traps, feedback loops, dissipative conditions–the landscape expands system‐level properties emerge, including transient catalysis, metabolic self‐replication, Darwinian‐like evolution. Controlling these at biointerface would facilitate intelligent therapeutic interventions anti‐tumor phototherapy. Supramolecular chemistry provides valuable framework exploring new physicochemical spaces porphyrins, may offer distinct advantages extensive applications across diverse fields.

Язык: Английский

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Exploring the programmability of autocatalytic chemical reaction networks

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 27, 2024

Язык: Английский

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