When contemplating the inside of a bacterial cell, most researchers assume it behaves like a fluid-filled sac. Not a water balloon exactly—the cytoplasm is too chock-full of macromolecules to behave like water—but something more viscous, like a balloon filled with glycerol.
The implication here is that the cell is effectively homogeneous with enzymes and metabolites freely diffusing and that their concentrations are the key to reaction kinetics. At least this is the way biochemists traditionally have modeled the cell.
As it turns out, that model is overly simplistic. In a new study, researchers demonstrated that bacterial cytoplasm actually is more akin to glass—or, rather, a glass-forming liquid very near to the so-called glass transition. In this environment, relatively small molecules and proteins appear to move by diffusion. Particles larger than about 30 nm, the size of a ribosome, move far more slowly, a result of the fluid’s glass-like properties. Even more remarkably, metabolic activity appears to “fluidize” the cytoplasm, making it possible for larger particles to move more freely in a metabolically active cell than in a dormant one.
That observation, which reconciles previous conflicting data on cytoplasmic motion, has wide-ranging implications for processes ranging from the movement of chromosomes and plasmids during partitioning, to the assembly of virus particles, said Christine Jacobs-Wagner, Professor of Molecular, Cellular and Developmental Biology at Yale University and an Investigator of the Howard Hughes Medical Institute, who led the study which appeared in the January 16 issue of the journal Cell (1).
“If you affect cellular dynamics, you affect the physiology and the behavior of the cell, because all biological processes are affected,” Jacobs-Wagner said. “Biological macromolecules and complexes have to be able to move to function; they have to be able to find one another and interact.”
According to Jacobs-Wagner, the link between cytoplasmic fluid dynamics and metabolic activity was discovered by accident. A graduate student was using motion tracking to study a fluorescently tagged filament protein in the bacterium, Caulobacter crescentus. At first, the particles moved freely throughout the cell. But at some point, the student noticed the filament motion abruptly came to a halt. At the same time, the cells also stopped growing.
That observation, Jacobs-Wagner said, “blew our mind.” Suspecting that metabolic activity somehow was the key, the team applied treatments that would force the cells into dormancy, such as removing carbon sources or sapping ATP reserves. Those treatments caused the particles essentially to freeze in place, The team also observed similar behavior in a different bacterial species, Escherichia coli.
According to Jacobs-Wagner, viscosity isn’t sufficient to explain the behavior and dynamics of different particles. “If it were [a viscosity effect], small and big particles would see the environment the same way,” she said. “But larger particles perceive the environment differently than small particles, even though they are in the same environment.”
Instead, she said, the cytoplasm behaves like colloidal glass, an analogy that makes sense in light of how crowded the cytoplasm really is. (A colloidal glass is one in which a liquid containing a high concentration of particles begins to flow ever more slowly until it eventually stops moving altogether.)
And, similar to glass-like liquids near the glass transition, the cytoplasm appears to be highly sensitive to perturbation. In colloidal glasses, Jacobs-Wagner said, physical agitation can fluidize the system. It is possible, she explained, that biochemical activity does the same thing in the cell by essentially shaking up jammed components, causing them to rearrange and move large distances.
Hugues Berry, a Senior Researcher at the French National Institute for Research in Computer Science & Control (INRIA) and the University of Lyon, who studies intracellular dynamics using mathematical modeling, said the findings potentially explain bacterial dormancy.
“Let’s say that your metabolism is high and you have many, many reactions occurring, and then suddenly you cut off the food source and you have to stop metabolic activity,” Berry said. “You have to cool down your metabolism. How do you do that? One way to cool down is to hinder molecular encounters.”
Alternatively, he suggested, this glass-like behavior could provide a mechanism for producing distinct molecular environments in cells that have no internal membranes.
Whatever the reason, it’s now clear that the bacterial cytoplasm is more complicated than a water balloon. “Our study is raising a lot more questions than it is answering,” Jacobs-Wagner said. “But it makes us think the cytoplasm has a different physical nature than we often assume.”
1. Parry, B.R., et al., “The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity,” Cell, 156:183–94, 2014.