Amoebas get social when they hit hard times

Editor’s Note: This article was written by Rezina Siddique, a Ph.D. student in Biomedical Engineering at Johns Hopkins with an M.S. in Nanoscale Science and Engineering, and first appeared in the 2013 issue of Nano-Bio Magazine. 

How single-celled social amoebae respond to chemical signals is shedding light on the processes and behavior of more complex organisms, including mammals. A recent paper suggests that there is a mechanism by which amoeba amplify a desirable chemical stimulus in order to self-organize and collectively migrate.

Amoeba are single-celled organisms with the capability to aggregate to form a multi-cellular organism, and later to a fruiting body. Andre Levchenko, professor of biomedical engineering and affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology, used the social amoeba, Dictyostelium discoideum, because as a multicellular organism it contains cells with different genotypes. Levchenko’s team sought to clarify how external signals were amplified by the organism to facilitate aggregation.

Dictyostelium discoideum slugs (bottom) and stalks with spore masses on top. Photo credit: Owen Gilbert

Dictyostelium discoideum slugs (bottom) and stalks with spore masses on top. Photo credit: Owen Gilbert

“The way [these organisms] detect signals and move are similar to how neutrophils, a natural part of our immune system, detect and move to the site of infection…They share the ability to migrate in a very directed way to get where they are needed,” said Levchenko. When resources are plentiful, Levchenko’s team found that Dicty are content in remain alone. But when food supplies run low, they gather into a multicellular slug.

As a slug, he said, “they can move together to find a more favorable location,” said Levchenko. The cell-cell communication that takes place during the transition relies on chemotaxis, which is the movement towards or away from a chemical stimulus along a concentration gradient. This behavior is similar in mammalian cells, relevant in both healthy and pathological conditions. Their results, are published in volume 5, issue 213 of Science Signaling.

Levchenko’s team developed a microfluidic pattern generating device that allows the user to control the environment and stimulus duration in a highly tunable way, while still being able to visualize cells under a microscope. Historically, Levchenko explained, these types of experiments were done with pipettes, but with the device his group was able to perform their experiments with the dynamic signaling responses consistent with the known behavior of the amoeba.

Previously, a mathematical model was developed to explain the mechanism of signal amplification that occurred in the amoeba, but there was no way to test it. However, using their microfluidic pattern generator, Levchenko’s group was able to validate the model experimentally. “Understanding the dynamics of chemotaxis within this system can shed insight into how other multicellular organisms, as well as how mammalian cells interact,” Levchenko said.

During aggregation, cyclic AMP (cAMP), a molecule that stimulates hunger, serves as chemoattractant. A starving social amoeba secretes cAMP to attract other amoebae to it, which all travel towards the central amoeba. These other cells also start releasing cAMP in a periodic fashion in order to amplify the signal and attract additional amoebae, creating a pulsating and wave-like signal. An individual cell ends up seeing waves of activity. This is similar to pacemaker cells in the heart, where periodic activity regulates cell behavior.

In a population of cells, some cells are more sensitive while others are less sensitive. This discrepancy is not visible when averaging the response over the entire population or when examining a single representative cell. By applying the hunger stimulus to cells within their device, Levchenko’s group found that there is a large difference across cells in a given population. Some cells did not respond at all, while others responded very strongly to the same stimulus. They also found that at higher doses, the majority of cells responded, while at lower doses, smaller numbers of cells responded. This indicates that the cells that respond strongly must have some ability to amplify the signal.

Differential sensitivity in the cells helps them to organize. Adaptation allows them to transiently suppress their sensitivity long enough to be able to form a multi-cellular organism. The adaptive and amplification properties of the amoeba resemble what occurs in bacterial chemotaxis. The results have implications for the study of cell decision making versus commitment to behavior within cells of a given tissue, or different types of cells that work together.

Editor’s Note: This article was written by Rezina Siddique, a Ph.D. student in Biomedical Engineering at Johns Hopkins with an M.S. in Nanoscale Science and Engineering, and first appeared in the 2013 issue of Nano-Bio Magazine.