Crowded into Cells

How did the earliest molecules evolve into the complex packages of life that we call cells? A chemical model developed by Penn State researchers may explain some steps along the way.

Using large “macromolecules” called polymers, professors of chemistry Christine Keating and Philip Bevilacqua, and their graduate students Christopher Strulson and Rosalynn Molden, created primitive cell-like structures and infused them with RNA—the genetic coding material that is thought to precede the appearance of DNA on Earth. They then demonstrated how these molecules would react chemically under conditions that might have been present on the early Earth.

RNA strands and RNA enzymes coming together within droplets of dextran
C. A. Strulson, Penn State

To test how early cell-like structures could have formed and acted to compartmentalize RNA molecules even in the absence of lipid-like molecules that make up modern cellular membranes, Penn State scientists generated simple, non-living model "cells" in the laboratory. Shown are RNA strands (blue) and RNA enzymes (red) coming together within droplets of dextran.

In modern biology all life, with the exception of some viruses, uses DNA as its genetic storage mechanism. According to the “RNA-world” hypothesis, RNA appeared on Earth first, serving as both the genetic-storage material and the functional molecules for catalyzing chemical reactions. DNA and proteins evolved much later.

“A missing piece of the RNA-world puzzle is compartmentalization,” Bevilacqua notes. “It’s not enough to have the necessary molecules that make up RNA floating around; they need to be compartmentalized and they need to stay together without diffusing away. This packaging needs to happen in a small-enough space—something analogous to a modern cell—because a simple fact of chemistry is that molecules need to find each other for a chemical reaction to occur.”

To test how early cell-like structures could have formed and compartmentalized RNA molecules even in the absence of the lipid-like molecules that make up modern cellular membranes, Strulson and Molden generated simple, non-living model “cells” using solutions of two polymers: polyethylene glycol (PEG) and dextran. “These solutions form distinct polymer-rich aqueous compartments, into which molecules like RNA can become locally concentrated,” Keating explains.

Once the RNA was packed into the dextran-rich compartments, the team found the molecules were able to associate physically, resulting in chemical reactions. “The more densely the RNA was packed, the more quickly the reactions occurred,” Bevilacqua says. “We noted an increase in the rate of chemical reactions of up to about 70-fold.”

“Most importantly,” he adds, “we showed that for RNA to ‘do something’—to react chemically—it has to be compartmentalized tightly into something like a cell. Our experiments have shown that some compartmentalization mechanism may have provided catalysis in an early-Earth environment.”

Keating notes that although she and Bevilacqua do not suggest that PEG and dextran were the specific polymers present on the early Earth, these polymers do provide a clue to a plausible route to compartmentalization: phase separation.

“Phase separation occurs when different types of polymers are present in solution at relatively high concentrations,” she explains. “Instead of mixing, the sample separates to form two distinct liquids, similar to how oil and water separate,’ she says. “The aqueous-phase compartments we manufactured can drive biochemical reactions by increasing local reactant concentrations. It’s possible that some other sorts of polymers might have been the molecules that drove compartmentalization on the early Earth."

The team also found that the longer the string of RNA, the more densely it would be packed into the dextran compartment of the ATPS, while the shorter strings tended to be left out. “We hypothesize that this might indicate some kind of primitive sorting method,” Bevilacqua says.

He and Keating hope to continue their investigations by testing their model-cell with other polymers.

“We are interested in looking at compartmentalization in polymer systems that are more closely related to those that may have been present on the early Earth,” Keating says, “and also those that may be present in contemporary biological cells, where RNA compartmentalization remains important for a wide range of cellular processes.”

Christine Keating, Ph.D., and Philip Bevilacqua, Ph.D., are professors of chemistry, and can be reached at cmd8@psu.edu and pcb5@psu.edu. Christopher Strulson and Rosalynn Molden are graduate students in chemistry. The journal Nature Chemistry posted an article based on this research as an advance online publication on October 14, 2012. The research was funded by the National Science Foundation.

Last Updated December 13, 2012