arXiv subjects

Jack W. Szostak

Publications and source records attributed to Jack W. Szostak.

6 recordsLinked to original sources

arXiv2026

Conditioning as a route to stereotyped behavior in growing populations

Biological systems perform complex multi-step processes in a reproducible way despite underlying stochasticity. The standard explanation is micromanagement by molecular machinery that recognizes and corrects specific errors. Here we study conditioning, a qualitatively different strategy in which attempts failing a coarse criterion are destroyed and do not leave a physical record. The surviving, i.e., conditioned, ensemble is narrower and therefore more ordered. We model conditioning through stochastic resets in a ''socks-before-shoes'' model of a growing population, where $n$ actions must be completed in any order to replicate and any replication attempt not finished by a threshold time is discarded. We find that resets impose hierarchical temporal ordering of the $n$ actions without microscopic control over which action happens when. When disorder carries a sufficient time penalty, this ordering is free: the fastest-growing population is automatically the most ordered, with no direct selection for order required. Save points, at which verified progress is preserved across resets, allow conditioning to scale to complex multi-step processes. Conditioning provides a minimal route to reliable behavior, requiring only a clock rather than molecular machinery that recognizes specific errors. For the right class of processes, it pays for itself.

q-bio.PE↗

arXiv2025

Suppression of errors in collectively coded information

Modern life largely transmits genetic information from mother to daughter through the duplication of single physically intact molecules that encode information. However, copying an extended molecule requires complex copying machinery and high fidelity that scales with the genome size to avoid the error catastrophe. Here, we explore these fidelity requirements in an alternative architecture, the virtual circular genome, in which no one physical molecule encodes the full genetic information. Instead, information is encoded and transmitted in a collective of overlapping and interacting segments. Using a model experimental system of a complex mixture of DNA oligomers that can partly anneal and extend off each other, we find that mutant oligomers are suppressed relative to a model without collective encoding. Through simulations and theory, we show that this suppression of mutants can be explained by competition for productive binding partners. As a consequence, information can be propagated robustly in a virtual circular genome even at mutation rates expected under prebiotic conditions.

q-bio.PE↗

arXiv2025

Simple lipids form stable higher-order structures in concentrated sulfuric acid

Venus has become a target of astrobiological interest because it is physically accessible to direct exploration, unlike exoplanets. So far this interest has been motivated not by the explicit expectation of finding life but rather by a desire to understand the limits of biology. The venusian surface is sterilizing, but the cloud deck includes regions with temperatures and pressures conventionally considered compatible with life. However, the venusian clouds are thought to consist of concentrated sulfuric acid. To determine if any fundamental features of life as we understand them here on Earth could in principle exist in these extreme solvent conditions, we tested several simple lipids for resistance to solvolysis and their ability to form structures in concentrated sulfuric acid. We find that single-chain saturated lipids with sulfate, alcohol, trimethylamine, and phosphonate head groups are resistant to sulfuric acid degradation at room temperature. Furthermore, we find that they form stable higher-order structures typically associated with lipid membranes, micelles, and vesicles. Finally, results from molecular dynamics simulations suggest a molecular explanation for the observed robustness of the lipid structures formed in concentrated sulfuric acid. We conclude with implications for the study of Venus as a target of experimental astrobiology.

physics.chem-ph↗

arXiv2025

A minimal scenario for the origin of non-equilibrium order

Life uses non-equilibrium mechanisms to create ordered structures not attainable at equilibrium; the resulting order is assumed to provide functional benefits that outweigh costs of time and energy needed by these mechanisms. Here, we show that models of DNA replication and self-assembly, when expanded to include known stalling effects, can evolve error correcting mechanisms like kinetic proofreading and dynamic instability through selection for fast replication alone. We abstract these results into a general framework that predicts a counterintuitive ''order through speed'' effect if the distribution of replication times is wide enough. We test our results against recent mutational screens of proofreading polymerases. Our work suggests the intriguing possibility that non-equilibrium order can evolve even before that order is directly functional, with consequences for the evolution of mutation rates, viral capsid assembly, and the origin of life.

q-bio.PE↗

arXiv2023

Lipid exchange promotes fusion of model protocells

Vesicle fusion is an important process underlying cell division, transport, and membrane trafficking. In phospholipid systems, a range of fusogens including divalent cations and depletants have been shown to induce adhesion, hemifusion, and then full content fusion between vesicles. This works shows that these fusogens do not perform the same function for fatty acid vesicles, which are used as model protocells (primitive cells). Even when fatty acid vesicles appear adhered or hemifused to each other, the intervening barriers between vesicles do not rupture. This difference is likely because fatty acids have a single aliphatic tail, and are more dynamic than their phospholipid counterparts. To address this, we postulate that fusion could instead occur under conditions, such as lipid exchange, that disrupt lipid packing. Using both experiments and molecular dynamics simulations, we verify that fusion in fatty acid systems can indeed be induced by lipid exchange. These results begin to probe how membrane biophysics could constrain the evolutionary dynamics of protocells.

cond-mat.soft↗

arXiv2020

Bulk self-assembly of giant, unilamellar vesicles

The desire to create cell-like models for fundamental science and applications has spurred extensive effort towards creating giant unilamellar vesicles (GUVs). However, a route to selectively self-assemble GUVs in bulk has remained elusive. In bulk solution, membrane-forming molecules such as phospholipids, single-tailed surfactants, and block copolymers typically self-assemble into multilamellar, onion-like structures. So although self-assembly processes can form nanoscale unilamellar vesicles, scaffolding by droplets or surfaces is required to create GUVs. Here we show that surprisingly, it is possible to bulk self-assemble cell-sized GUVs with almost complete selectivity over other vesicle topologies. The seemingly paradoxical pair of features that enables this appears to be having very dynamic molecules at the nanoscale, that create unusually rigid membranes. The resultant self-assembly pathway enables encapsulation of molecules and colloids, and can also generate model primitive cells that can grow and divide.

cond-mat.soft↗