Membrane or metabolism, which came first?

LMU researchers have demonstrated a possible mechanism for metabolic processes without cell membranes in water-filled pores.

Looking at life today, it is difficult to imagine how complex biological processes and structures could have developed from simple building blocks. All cellular processes and reactions appear to be closely interdependent and necessarily occur within a cell membrane. There is no known organism that deviates from this pattern. But how did it come about?

How does a cell membrane form without metabolism? Or conversely, how does metabolism arise without a cell membrane? This classic chicken-and-egg problem is addressed in a recent study published in Nature Physics by researchers from LMU professor Dieter Braun’s team.

Cells without a membrane

In their article, the researchers show that simple heat flow across thin, water-filled pores can accumulate a wide variety of molecules with different chemical and physical properties, and allow these molecules to interact and form reactions in a confined space, even in the absence of a cell membrane. In this very simple protocell, there is a thermal gradient that takes over the functions of a cell membrane, but not yet any physical boundary between the reaction and the diluted water.

“Our investigations show that this simple physical mechanism, which would have been very common on early Earth, can perform many functions that would normally require a cell membrane,” says principal investigator of the study, Dieter Braun. The results suggest that heated rock pores could have been the natural setting in which biological cells emerged.

Origin of life simulated in the laboratory

When a temperature gradient is applied across a thin, water-filled pore, most of the diluted molecules accumulate at the bottom of thpore, toward the cold side. The team simulated this environment in the laboratory using custom-made chambers consisting of a thin sheet of water, sandwiched between optically transparent plates.

For the experiment, the researchers tested the circumstances under which a so-called superfolder green fluorescent protein (sfGFP) is produced. The mixture in the chambers contained over 100 different components, ranging from amino acids and nucleotides – the building blocks of proteins and RNA – to ribosomes and polymerases – highly specialized molecular machines present in all living organisms.

“When overly diluted, the reaction becomes inactive and cannot produce the marker protein,” says Braun. Upon incubation in a ‘thermal chamber,’ however, the components accumulate to a sufficient level to enable the reaction to get going and synthesize sfGFP.

New possibilities for biotechnology

“While the experimental design is currently limited by the physical parameters of the chamber, as well as the temperature difference that can be achieved, this would not have been an issue on early Earth, where the ubiquitous presence of water-filled pores of all shapes and sizes would have provided ample variety in terms of prebiotic reaction containers,” says Alexander Floroni, lead author of the paper.

The findings provide new insights into the possibility of metabolism prior to encapsulation in membranes and the emergence of cellular life. Moreover, they offer new approaches to biotechnology for the creation of synthetic living entities in the laboratory. “Before now, creating a synthetic cell that feeds itself across the membrane and implements cell division for growth was a major obstacle,” explains Braun. “Our research shows how we could get around this obstacle in the future.”