2013 Johns Hopkins Nano-Bio Magazine

Page 11

Amoebas Get Social When Times Get Tough By Rezina Siddique

How single-celled social amoebae respond to chemical signals is

mechanism of signal amplification that occurred in the amoeba,

shedding light on the processes and behavior of more complex

but there was no way to test it. However, using their microfluidic

organisms, including mammals. A recent paper suggests that there

pattern generator, Levchenko’s group was able to validate the

is a mechanism by which amoeba amplify a desirable chemical

model experimentally. “Understanding the dynamics of chemotaxis

stimulus in order to self-organize and collectively migrate.

within this system can shed insight into how other multicellular

Amoeba are single-celled organisms with the capability to ag-

organisms, as well as how mammalian cells interact,” Levchenko said.

gregate to form a multi-cellular organism, and later to a fruiting

During aggregation, cyclic AMP (cAMP), a molecule that

body. Andre Levchenko, professor of biomedical engineering and

stimulates hunger, serves as chemoattractant. A starving social

affiliated faculty member of Johns Hopkins Institute for NanoBio-

amoeba secretes cAMP to attract other amoebae to it, which all

Technology, used the social amoeba, Dictyostelium discoideum,

travel towards the central amoeba. These other cells also start

because as a multicellular organism it contains cells with different

releasing cAMP in a periodic fashion in order to amplify the signal

genotypes. Levchenko’s team sought to clarify how external signals

and attract additional amoebae, creating a pulsating and wave-like

were amplified by the organism to facilitate aggregation.

signal. An individual cell ends up seeing waves of activity. This

“The way [these organisms] detect signals and move are similar to how neutrophils, a natural part of our immune system, detect

is similar to pacemaker cells in the heart, where periodic activity regulates cell behavior.

and move to the site of infection…They share the ability to migrate

In a population of cells, some cells are more sensitive while oth-

in a very directed way to get where they are needed,” said Levchen-

ers are less sensitive. This discrepancy is not visible when averaging

ko. When resources are plentiful, Levchenko’s team found that

the response over the entire population or when examining a single

Dicty are content in remain alone. But when food supplies run

representative cell. By applying the hunger stimulus to cells within

low, they gather into a multicellular slug.

their device, Levchenko’s group found that there is a large differ-

As a slug, he said, “they can move together to find a more favor-

ence across cells in a given population. Some cells did not respond

able location,” said Levchenko. The cell-cell communication that

at all, while others responded very strongly to the same stimulus.

takes place during the transition relies on chemotaxis, which is the

They also found that at higher doses, the majority of cells re-

movement towards or away from a chemical stimulus along a con-

sponded, while at lower doses, smaller numbers of cells responded.

centration gradient. This behavior is similar in mammalian cells,

This indicates that the cells that respond strongly must have some

relevant in both healthy and pathological conditions. Their results,

ability to amplify the signal.

are published in volume 5, issue 213 of Science Signaling.

Differential sensitivity in the cells helps them to organize. Ad-

Levchenko’s team developed a microfluidic pattern generating

aptation allows them to transiently suppress their sensitivity long

device that allows the user to control the environment and stimulus

enough to be able to form a multi-cellular organism. The adaptive

duration in a highly tunable way, while still being able to visualize

and amplification properties of the amoeba resemble what occurs

cells under a microscope. Historically, Levchenko explained, these

in bacterial chemotaxis. The results have implications for the study

types of experiments were done with pipettes, but with the device

of cell decision making versus commitment to behavior within cells

his group was able to perform their experiments with the dynamic

of a given tissue, or different types of cells that work together.

signaling responses consistent with the known behavior of the amoeba. Previously, a mathematical model was developed to explain the

Rezina Siddique is a Ph.D. student in Biomedical Engineering at Johns Hopkins with an M.S. in Nanoscale Science and Engineering.

Spring 2013

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