Toward synthetic life—Emergence, growth, creation of offspring, decay, and rescue of fuel-dependent synthetic cells DOI Creative Commons
Monika Wenisch,

Yinqing Li,

Marius G. Braun

et al.

Chem, Journal Year: 2025, Volume and Issue: unknown, P. 102578 - 102578

Published: May 1, 2025

Language: Английский

Open questions on liquid–liquid phase separation DOI Creative Commons
Evan Spruijt

Communications Chemistry, Journal Year: 2023, Volume and Issue: 6(1)

Published: Feb. 3, 2023

Liquid-liquid phase separation (LLPS) underlies the formation of intracellular membraneless compartments in biology and may have played a role protocells that concentrate key chemicals during origins life. While LLPS simple systems, such as oil water, is well understood, many aspects complex, out-of-equilibrium molecular systems remain elusive. Here, author discusses open questions recent insights related to formation, function fate condensates both cell protocell research.

Language: Английский

Citations

43

How Droplets Can Accelerate Reactions─Coacervate Protocells as Catalytic Microcompartments DOI Creative Commons
Iris B. A. Smokers, Brent S. Visser, Annemiek D. Slootbeek

et al.

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(14), P. 1885 - 1895

Published: July 5, 2024

ConspectusCoacervates are droplets formed by liquid–liquid phase separation (LLPS) and often used as model protocells–primitive cell-like compartments that could have aided the emergence of life. Their continued presence membraneless organelles in modern cells gives further credit to their relevance. The local physicochemical environment inside coacervates is distinctly different from surrounding dilute solution offers an interesting microenvironment for prebiotic reactions. Coacervates can selectively take up reactants enhance effective concentration, stabilize products, destabilize lower transition states, therefore play a similar role micellar catalysts providing rate enhancement selectivity reaction outcome. Rate must been essential origins life enabling chemical reactions occur at appreciable rates overcoming competition hydrolysis.In this Accounts, we dissect mechanisms which coacervate protocells accelerate provide selectivity. These similarly be exploited control cellular processes. First, affect concentration copartitioning or exclusion product inhibitor. Second, change energy landscape taking place droplets. more apolar than rich charged moieties, stability reactants, states products. crowded nature favor complexation large molecules such ribozymes. locally proton water activity facilitate involving (de)protonation step, condensation sensitive hydrolysis. Not only core, but also surface provides site with gradients pH, charge. catalytic amino acids localize like divalent metal ions, leading Lastly, these properties certain pathways, thereby give over outcome.These illustrated case study on ribozyme coacervates, there fine balance between reactivity tuned composition. Furthermore, both catalyze selectivity, demonstrating functioned enzyme-like microcompartments

Language: Английский

Citations

21

Self-assembly of stabilized droplets from liquid–liquid phase separation for higher-order structures and functions DOI Creative Commons
Mehwish Naz,

Lin Zhang,

Chong Chen

et al.

Communications Chemistry, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 9, 2024

Dynamic microscale droplets produced by liquid-liquid phase separation (LLPS) have emerged as appealing biomaterials due to their remarkable features. However, the instability of limits construction population-level structures with collective behaviors. Here we first provide a brief background in context materials properties. Subsequently, discuss current strategies for stabilizing including physical and chemical modulation. We also recent development LLPS various applications such synthetic cells biomedical materials. Finally, give insights on how stabilized can self-assemble into higher-order displaying coordinated functions fully exploit potentials bottom-up biology applications.

Language: Английский

Citations

17

A roadmap toward the synthesis of life DOI Creative Commons
Christine M. E. Kriebisch, Olga Bantysh, Lorena Baranda Pellejero

et al.

Chem, Journal Year: 2025, Volume and Issue: unknown, P. 102399 - 102399

Published: Feb. 1, 2025

Language: Английский

Citations

3

Probing the surface charge of condensates using microelectrophoresis DOI Creative Commons
Merlijn H. I. van Haren, Brent S. Visser, Evan Spruijt

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 26, 2024

Abstract Biomolecular condensates play an important role in cellular organization. Coacervates are commonly used models that mimic the physicochemical properties of biomolecular condensates. The surface plays a key governing molecular exchange between condensates, accumulation species at interface, and stability against coalescence. However, most properties, including charge zeta potential, remain poorly characterized understood. potential coacervates is often measured using laser doppler electrophoresis, which assumes size-independent electrophoretic mobility. Here, we show this assumption incorrect for liquid-like present alternative method to study mobility vitro condensate by microelectrophoresis single-particle tracking. have size-dependent mobility, originating from their fluid nature, well-defined calculated. Interestingly, measurements reveal polylysine chains enriched polylysine/polyaspartic acid complex coacervates, causes negatively charged protein ɑ-synuclein adsorb accumulate interface. Addition ATP inverts charge, displaces may help suppress its interface-catalyzed aggregation. Together, these findings how can be altered, making platform combined with automated tracking promising characterization technique both coacervate protocells.

Language: Английский

Citations

13

Recent advances in coacervation and underlying noncovalent molecular interaction mechanisms DOI Creative Commons

Qiongyao Peng,

Tao Wang, Diling Yang

et al.

Progress in Polymer Science, Journal Year: 2024, Volume and Issue: 153, P. 101827 - 101827

Published: May 8, 2024

Coacervation is a liquid-liquid phase separation phenomenon. It involves the formation of dense coacervate phase, rich in concentrated materials, and co-existing immiscible dilute supernatant. This phenomenon can occur either from homogeneous aqueous solution (simple coacervation) or when two different macromolecular solutions (proteins, polymers, colloids) are brought into contact (complex coacervation). has historical significance as it may have played role origin life, concentrating nutritious materials through separation. also reveals underlying mechanisms many biological phenomena such intracellular biomolecular condensates, extracellular matrices, squid beak's gradient properties, sessile organism's wet adhesion, Alzheimer's diseases, more. provides insights inspires promising areas like artificial cells/tissues, gene/drug delivery, underwater adhesives, beyond. The driving forces coacervation noncovalent molecular interactions, often referred to 'chemistry beyond molecule', including hydrophobic interaction, electrostatic hydrogen-bonding cation-π π-π multivalency, etc. In this work, we systematically reviewed interactions simple complex coacervation, respectively. We summarize commonly used their corresponding structures, discussing applications. Some remaining challenge issues perspectives for future studies presented. Understanding alongside compositions better guide design novel elucidate various phenomena, contribute development optimization relevant engineering technologies.

Language: Английский

Citations

13

Template-based copying in chemically fuelled dynamic combinatorial libraries DOI Creative Commons
Christine M. E. Kriebisch, Ludwig Burger, Oleksii Zozulia

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1240 - 1249

Published: July 16, 2024

Abstract One of science’s greatest challenges is determining how life can spontaneously emerge from a mixture molecules. A complicating factor that and its molecules are inherently unstable—RNA proteins prone to hydrolysis denaturation. For the de novo synthesis or better understand emergence at origin, selection mechanisms needed for unstable Here we present chemically fuelled dynamic combinatorial library model RNA oligomerization deoligomerization shine new light on purification under kinetic control. In experiments, oligomers only be sustained by continuous production. Hybridization powerful tool selecting molecules, offering feedback rates. Moreover, find templation used purify libraries oligomers. addition, template-assisted formation within coacervate-based protocells changes compartment’s physical properties, such as their ability fuse. Such reciprocal coupling between oligomer production properties key step towards synthetic life.

Language: Английский

Citations

12

Materials Inspired by Living Functions DOI Creative Commons
Mauri A. Kostiainen, Arri Priimägi, Jaakko V. I. Timonen

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(37)

Published: March 19, 2024

Abstract Engineering or mimicking living materials found in nature has the potential to transform use of materials. Unlike classic synthetic which are typically optimized for static properties, economics, and recently also sustainability, life dynamic, feedback‐controlled, evolving, adaptive. Although do not exhibit such complicated functionalities, researchers increasingly challenging this viewpoint expanding material concepts toward dynamic systems inspired by selected life‐like functions. Herein, it is suggested that can be approached from two perspectives: through engineering biological organisms their functions provide basis new materials, producing with rudimentary life‐inspired Current advances discussed perspectives (i) features based on built‐in memory associative learning, (ii) emergent structures self‐regulated designs using non‐equilibrium systems, (iii) interfacing non‐living form cellular community control growth open routes fabrication. Strategies combining (i)–(iii) responses applications interactive autonomous devices, helping realize next‐generation sensors, soft robots, external over bioproduction self‐organizing structural

Language: Английский

Citations

10

Selective peptide bond formation via side chain reactivity and self-assembly of abiotic phosphates DOI Creative Commons
Arti Sharma, Kun Dai, Mahesh D. Pol

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Abstract In the realm of biology, peptide bonds are formed via reactive phosphate-containing intermediates, facilitated by compartmentalized environments that ensure precise coupling and folding. Herein, we use aminoacyl phosphate esters, synthetic counterparts biological adenylates, drive selective bond formation through side chain-controlled reactivity self-assembly. This strategy results in preferential incorporation positively charged amino acids from mixtures containing natural non-natural during spontaneous amide water. Conversely, esters lack assembly exhibit fast result random coupling. By introducing structural modifications to (ethyl vs . phenyl) while retaining aggregation, able tune selectivity incorporating aromatic acid residues. approach enables synthesis sequences tailored specific overcoming limitations posed certain combinations. Furthermore, demonstrate a balance between electrostatic stacking interactions facilitates covalent self-sorting or co-assembly oligomerization reactions using unprotected N-terminus esters. These findings suggest self-assembly abiotic can activate selection mechanism enabling departure randomness autonomous

Language: Английский

Citations

1

DNA Droplets: Intelligent, Dynamic Fluid DOI Creative Commons
Hirotake Udono, Jing Gong, Yusuke Sato

et al.

Advanced Biology, Journal Year: 2022, Volume and Issue: 7(3)

Published: Dec. 5, 2022

Abstract Breathtaking advances in DNA nanotechnology have established as a promising biomaterial for the fabrication of programmable higher‐order nano/microstructures. In context developing artificial cells and tissues, droplets emerged powerful platform creating intelligent, dynamic cell‐like machinery. are microscale membrane‐free coacervate formed through phase separation. This new type system couples fluid‐like property with long‐established programmability. hybrid nature offers an advantageous route to facile robust control over structures, functions, behaviors droplets. review begins by describing condensation, commenting on physical properties strategies hydrogels By presenting overview development pathways leading droplets, it is shown that technology has evolved from static, rigid systems soft, systems. Next, basic characteristics described fluid showcasing latest examples highlighting their distinctive features related sequence‐specific interactions mechanical properties. Finally, this discusses potential challenges numerical modeling able connect link between individual sequences macroscopic

Language: Английский

Citations

31