Thermally Driven Membrane Phase Transitions Enable Content Reshuffling in Primitive Cells.

Francesca Coscia,Lorenzo Di Michele,Pietro Cicuta,Anna Wang,Claudia Bonfio,Gianluca Petris,Roger Rubio-Sánchez,Derek K O’Flaherty

doi:10.1021/jacs.1c06595

Abstract

Self-assembling single-chain amphiphiles available in the prebiotic environment likely played a fundamental role in the advent of primitive cell cycles. However, the instability of prebiotic fatty acid-based membranes to temperature and pH seems to suggest that primitive cells could only host prebiotically relevant processes in a narrow range of nonfluctuating environmental conditions. Here we propose that membrane phase transitions, driven by environmental fluctuations, enabled the generation of daughter protocells with reshuffled content. A reversible membrane-to-oil phase transition accounts for the dissolution of fatty acid-based vesicles at high temperatures and the concomitant release of protocellular content. At low temperatures, fatty acid bilayers reassemble and encapsulate reshuffled material in a new cohort of protocells. Notably, we find that our disassembly/reassembly cycle drives the emergence of functional RNA-containing primitive cells from parent nonfunctional compartments. Thus, by exploiting the intrinsic instability of prebiotic fatty acid vesicles, our results point at an environmentally driven tunable prebiotic process, which supports the release and reshuffling of oligonucleotides and membrane components, potentially leading to a new generation of protocells with superior traits. In the absence of protocellular transport machinery, the environmentally driven disassembly/assembly cycle proposed herein would have plausibly supported protocellular content reshuffling transmitted to primitive cell progeny, hinting at a potential mechanism important to initiate Darwinian evolution of early life forms.

Highlights

The emergence of primitive cell cycles represents a step toward the generation of model protocells
One unresolved difficulty with proposing primitive cell cycles is that prebiotic components should be employed, and the identified model conditions should be compatible with the prebiotic environment and processes
Such a model of primitive cell cycle relies on two assumptions: (i) that the required environmental conditions are not subject to fluctuations, as not to destabilize fatty acid vesicles, and (ii) that content reshuffling, product dilution, or substrate uptake is not required for encapsulated prebiotic reactions to work

Summary

■ INTRODUCTION

The emergence of primitive cell cycles represents a step toward the generation of model protocells. When a mixed sample of different protocells undergoes thermal cycling, the newly generated vesicles incorporate both RNA strands, efficiently assembling the Broccoli aptamer, which enhances the fluorescent signal of the DFHBI fluorogen (Figure 4e) Together, these results provide strong evidence that thermally driven pH variations can drive reversible and tunable lipid phase transitions and support the release and reshuffling of protocellular content, providing a prebiotically plausible possible mechanism for the emergence of a new generation of protocells with potentially enhanced functionalities

■ DISCUSSION

■ ACKNOWLEDGMENTS

■ REFERENCES