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Dynamic Growth and Replication in Coacervate Protocells

Project description

Growth and replication of model protocells

Growth and division are fundamental properties of living organisms. Understanding how a mixture of molecules can assemble into a replicating cell remains one of the biggest mysteries in the origin of life. The EU-funded project DynaGrow is going to develop a new kind of coacervate-based protocell model that can support growth and template-directed replication. These coacervate-based protocells are condensed water-rich liquid droplets that can compartmentalise and concentrate water-soluble template molecules. They will be composed of low-complexity oligopeptides capable of fuel-driven active growth achieved through elongation or side chain modification. This remarkable new approach represents a new step in the creation of a minimal cell, which is necessary for our understanding of the origin of life and evolution.

Objective

Replication and division are two of the most fundamental properties of living systems. Without replication, Darwinian evolution would not be possible, and life could never have reached the degree of complexity we see today. However, exactly how mixtures of non-living molecules developed the ability to replicate and divide, remains one of the biggest mysteries in modern science. Various molecular replicators have been investigated previously, but they are all destined to become extinct by dilution, since they lack a surrounding compartment that divides spontaneously during replication.

In this proposal, we aim at developing a new class of coacervate-based protocells that are capable of active growth and template-directed replication. The coacervates we propose here are condensed liquid droplets with a unique dual role: they act as a compartment that holds together and concentrates the template molecules and the building blocks, and they provide the right chemical environment for the replication reactions to take place at an appreciable rate. The coacervate-based protocells are composed of oligopeptides with low complexity sequences, inspired by the intrinsically disordered proteins found in membrane-free organelles inside cells. Active growth is achieved through fuel-driven reactions, either by elongation of existing peptides or by specific chemical modifications at the peptide side chains that enhance their coacervation potential. Longer peptides can also act as templates for conjugation of end-functionalized peptide fragments with sequence patterns complementary to the template. Protocells with sufficiently high growth or replication rates are not only stable against Ostwald ripening, but are also predicted to undergo spontaneous division through a shape instability. This would mark a key step in the emergence of minimal cells and open the way for the evolution of more complex life-like systems.

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Coordinator

STICHTING RADBOUD UNIVERSITEIT
Net EU contribution
€ 1 500 000,00
Address
Houtlaan 4
6525 XZ Nijmegen
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (1)