Dynamic Growth and Replication in Coacervate Protocells

ended

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.