We know that living cells – the type that can replicate and evolve into organisms – emerged from a soup of simple molecules. How they were able to do so, however, remains one of science’s greatest mysteries. “A fundamental question that has plagued chemistry and biology is how a self-replicating protocell could be formed out of a mixture of molecules,” says Evan Spruijt, an associate professor of Physical Organic Chemistry at Radboud University. With the support of the EU-funded PEPREP project, Spruijt, along with Manzar Abbas, a Marie Skłodowska-Curie fellow, are working to help unlock this mystery. To do so, they are developing protocells, cell-like compartments that can be made from simple molecules and that can mimic one or more key properties of living cells. “By developing these protocells, we hope to gain a better understanding of what is required to create a living cell from a soup of molecules,” explains Abbas.
An exciting new discovery
While other researchers have attempted to develop protocells, they’ve done so using relatively large and complex molecules, which were unlikely to have been around at the origins of life. Instead, this project decided to use peptides, a short chain of amino acids. “We chose peptides because they are simple and because they are one of the central building blocks of modern cells,” notes Spruijt. “By tuning the molecular details of these peptides, we hoped to get them to replicate themselves via a chemical reaction, ultimately resulting in a replicating protocell.” Although the researchers couldn’t get the peptides to self-replicate, their efforts did lead to an exciting new discovery. “It is known that coacervate droplets, the liquid droplets that peptide-based molecules form, can take up and concentrate a wide range of other relevant molecules,” says Abbas. “What we discovered is that this sequestration, combined with the unique chemical environment inside the droplets, can lead to enhanced chemical reactions.” According to Spruijt, this is the first time such a catalytic effect has been demonstrated. “If such a cell-like compartment can form spontaneously and catalyse important chemical reactions, it could give the compartment and the peptide forming it an evolutionary advantage – perhaps one that can help explain how self-replicating protocells were formed,” he adds.
One step closer…
Even though Spruijt and Abbas were unable to get peptides to self-replicate, they did manage to create protocells from a new type of peptide-based molecule. “Our design is one of the simplest molecules able to undergo liquid-liquid phase separation into small droplets, which act as cell-like compartments,” remarks Abbas. “As such, this design brings us one step closer to understanding the emergence of cells at the origins of life.” The project’s results have been published in several leading scientific journals, including ‘Nature Chemistry’.
PEPREP, protocells, cells, molecules, organisms