A simple physical mechanism enables homeostasis in primitive cells

• Published in: Nature chemistry 2016-05, Vol.8 (5), p.448-453
• Main Authors: Engelhart, Aaron E., Adamala, Katarzyna P., Szostak, Jack W.
• Format: Article
• Language: English
• Subjects: 639/638; 639/638/45/500; 639/638/45/607; 639/638/541/966; 639/638/92/500; Analytical Chemistry; Artificial Cells - chemistry; Biochemistry; Catalysis; Chemistry; Chemistry/Food Science; Enzymes; Evolution, Molecular; Fatty acids; Fatty Acids, Monounsaturated - chemistry; Homeostasis; Inorganic Chemistry; Monoglycerides - chemistry; Oligonucleotides - chemistry; Organic Chemistry; Physical Chemistry; RNA, Catalytic - antagonists & inhibitors; RNA, Catalytic - chemistry
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/nchem.2475

The emergence of homeostatic mechanisms that enable maintenance of an intracellular steady state during growth was critical to the advent of cellular life. Here, we show that concentration-dependent reversible binding of short oligonucleotides, of both specific and random sequence, can modulate ribozyme activity. In both cases, catalysis is inhibited at high concentrations, and dilution activates the ribozyme via inhibitor dissociation, thus maintaining near-constant ribozyme specific activity throughout protocell growth. To mimic the result of RNA synthesis within non-growing protocells, we co-encapsulated high concentrations of ribozyme and oligonucleotides within fatty acid vesicles, and ribozyme activity was inhibited. Following vesicle growth, the resulting internal dilution produced ribozyme activation. This simple physical system enables a primitive homeostatic behaviour: the maintenance of constant ribozyme activity per unit volume during protocell volume changes. We suggest that such systems, wherein short oligonucleotides reversibly inhibit functional RNAs, could have preceded sophisticated modern RNA regulatory mechanisms, such as those involving miRNAs. The development of cells requires a mechanism to support homeostasis—the maintenance of constant internal conditions—as cellular growth results in internal dilution. Now, a simple physical process is described in which short oligonucleotide inhibitors enable dilution-driven activation of encapsulated ribozymes via membrane growth, suggesting homeostatic mechanisms could have existed in the earliest cells.