Gravity plays a role in keeping cells small

Oct 25, 2013 by Anna Azvolinsky
Clifford Brangwynne (left), an assistant professor of chemical and biological engineering, and graduate student Marina Feric made a fundamental discovery about the likely role of gravity in limiting the size of cells. They conducted their experiments at Princeton's Hoyt Lab, which was recently renovated to support research in biological engineering. Credit: Frank Wojciechowski for the School of Engineering and Applied Science

(Phys.org) —The effects of gravity are relevant when building houses or flying airplanes, but biologists have generally accepted that the average cell is too small for gravity to play a role in how it is built or behaves. A finding by Princeton University researchers now shows gravity imposes a size constraint on cells. The results provide a novel reason why most animal cells are small and of similar size.

"Gravity becomes really important at a smaller scale than you might have guessed," said Clifford Brangwynne, an assistant professor of chemical and biological engineering who led the research.

While studying what makes large particles in a nucleus of the egg cells of the African clawed frog stay in place, Brangwynne and graduate student Marina Feric observed the particles falling to the bottom of the when a scaffolding inside the cells was disturbed.

The researchers, who published their findings in the October issue of Nature Cell Biology, concluded that when a cell reaches a certain size, it becomes subject to gravitational forces that require a scaffolding to stabilize the internal components.

"The research is really elegant and novel," said Zemer Gitai, an associate professor of molecular biology at Princeton, who was not involved in the research. "Cells almost certainly evolved to be [small enough] to ignore the effects of ."

This video is not supported by your browser at this time.
Researchers disrupted a chemical scaffold in the nucleus of a frog egg cell and observed what happened to the particles that were suspended in the nucleus. The video shows two types of bodies — called nucleoli (red) and histone locus bodies (green) — settling to the bottom of the nucleus. The researchers concluded that the scaffold, which is not present in smaller cells, is required to counteract the force of gravity once cells reach a certain size. Credit: Marina Feric and Clifford Brangwynne, Department of Chemical and Biological Engineering

The size is the limit

The typical animal cell has a diameter of about 10 microns (thousandths of millimeters). Larger cells, like the of the African clawed frog, are up to 1 millimeter in diameter, but examples of such large cells are not frequent. Scientists have attributed this size limit to the difficulty for large-volume cells to obtain nutrients, an explanation Brangwynne said is not backed by substantial evidence.

Brangwynne previously had shown that certain types of large particles within cells act like water droplets—they tend to merge upon contact. But in the nucleus, something was keeping them from fusing into one giant blob. The team first tested whether a scaffold was in place that allowed smaller particles to move through the mesh but caused larger particles to get stuck, preventing them from fusing. Feric tested this idea by injecting the frog egg nuclei with different sized Teflon-like beads and observed their movement. As predicted, small beads diffused throughout the nucleus but larger ones got stuck, providing evidence for a scaffold.

Feric next tested whether this matrix could be made up of fibers of the protein , which was known to form a cytoskeleton in the parts of cells outside of the nucleus but whose role in the nucleus was not clear.

The researchers rid the nuclei of the actin polymers, either by treating the nuclei with drugs against the protein, or by making the nucleus pump out the protein.

"When we did this experiment we found the large particles sunk like pebbles to the bottom of the nucleus. That was genuinely shocking," said Brangwynne.

Feric also attached a fluorescent probe to the actin proteins to visualize the matrix. The size of the holes of the mesh network matched the size predicted by the bead experiments.

Noting that actin is both less abundant in smaller nuclei and does not appear to form a mesh that spans the whole nucleus as it does in larger cells, Feric's experiments led the researchers to deduce that larger cells have the actin mesh to protect against gravity.

They propose that gravity becomes important at a certain particle density and a of roughly 10 microns—the size limit of most animal cells. The actin in these large nuclei keeps the particles in place as a support against gravity.

Particles in a cell become proportionally larger with increasing cell size. A particle in a small cell is like a single piece of dust—it floats well, unhindered by gravity. But particles in larger cells are like many pieces of dust clustered together that have a greater mass and require support to stay buoyed.

Tim Mitchison, who studies nuclear structure at Harvard Medical School, said the study shows new evidence that actin provides a supportive matrix in very large cells, but notes that is not clear whether these nuclei are a model for smaller cells.

The research provides a new function for actin in the nucleus, said Dyche Mullins, a molecular biologist at the University of California San Francisco School of Medicine. "The results suggest a large cell becomes fragile and needs a scaffold inside to support and separate the large number of it contains," he said.

Feric and Brangwynne plan to repeat the experiments in different-sized cells and explore the properties of the actin network in the nucleus to understand the limits of its strength.

Serendipitous discovery

The researchers said a rewarding aspect of the study was its surprising turns, which at one point led them to calculate the viscosity of the nucleus to understand the behavior of the beads they injected.

"We had absolutely no intention of trying to learn about gravity," said Brangwynne.

"That you need to know the viscosity of the cell to figure out that gravity could be important for setting the upper limits of cell size? It's hard to imagine how one could predict such a connection."

In an undergraduate course Brangwynne teaches, students have previously performed calculations suggesting gravity is a negligible force on . Brangwynne said he will now have to change the exercise. "This is where the research ends up influencing the class work."

Explore further: Identification of a plant-specific nanomachine regulating nuclear movement

More information: www.nature.com/ncb/journal/v15/n10/full/ncb2830.html

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katesisco
1 / 5 (12) Oct 25, 2013
Well, after the 65 my extinction event, the PETM of 9 my following had both high heat, and additional extinctions of the deep sea of foraminafera. http://en.wikiped...iki/PETM
The evidence shows many forms of life on the surface became minerature versions of what we see now.
Science maybe working toward the reason why small size and great heat occur after an extinction. Is it possible that the extinction is due to a sudden decrease in gravity creating impossible conditions for cellular life followed by the opposite, an increase in gravity limiting cellular size? Since it appears both these conditions moderate over time, perhaps we should point the finger at our Sol whose periods of magnetic reversal are known to include a temporary in-between status where two of the same magnetic pole exist for unknown periods of time.
jdbertron
1 / 5 (10) Oct 25, 2013
What a surprise. Unfortunately, gravity doesn't keep research budgets on dumb topics small.
HannesAlfven
1 / 5 (9) Oct 25, 2013
Re: "Is it possible that the extinction is due to a sudden decrease in gravity creating impossible conditions for cellular life followed by the opposite, an increase in gravity limiting cellular size?"

The details might not be perfectly dead-on, but I personally suspect that your logic is on the right general track. Contrary to what the textbooks say, there exists ample reason to suspect that G can and actually has changed. The most compelling evidence pertains to the delicate theoretical dance which scientists must jump through in order to justify the extraordinary sizes of the flying dinosaurs. They clearly go out of their way to favor the G-never-changes worldview, even though nobody can actually pin down the actual value of this constant.

See http://www.bearfa...ms.html.

See http://www.nature...30a.html for table of G measurements.

Also this: http://www.scienc...111.htm.
Torbjorn_Larsson_OM
5 / 5 (3) Oct 25, 2013
@katesisco: "Is it possible that the extinction is due to a sudden decrease in gravity creating impossible conditions for cellular life followed by the opposite, an increase in gravity limiting cellular size?"

No, Earth mass has stayed the same.

@HA: "Contrary to what the textbooks say, there exists ample reason to suspect that G can and actually has changed."

No there are no such reasons, which is what the textbooks describe (or they wouldn't be textbooks).

And you references gives no such reasons:
- The Nature article describes how the CODATA is consistent with a constant G, and how the new measurement methods have yet to be verified and accepted.
- The flyby data is neither consistent nor shown to be relevant for G.
- And your I assume pseudoscience link ("catastrophism" when evolution has shown it doesn't apply) doesn't show in my standard (Chrome) browser.
Q-Star
3.7 / 5 (3) Oct 25, 2013
They clearly go out of their way to favor the G-never-changes worldview, even though nobody can actually pin down the actual value of this constant.


Ya do realize the dispute involves plus or minus 10^minus15 ?

Want to see what the argument looks like in everyday numbers?

0,000000000006674215

Opposed to:

0.000000000006672346

I suppose those flying dinosaurs really needed that 0.02% difference to get off the ground, eh?
Torbjorn_Larsson_OM
5 / 5 (2) Oct 25, 2013
G-Star: That too. Add that the pseudoscience site was the first I've seen that Chrome can't display.

The flying non-avian dinosaur people is smoking something awfully strong.
Torbjorn_Larsson_OM
5 / 5 (2) Oct 25, 2013
@katesisco: By the way, your own link discusses possible hypotheses for the PETM. And it is unconnected with the KPh impactor extinction event.
Lurker2358
1 / 5 (8) Oct 25, 2013
I think the scientists were previously being idiots.

Of course gravity plays a role in cells.
dan42day
1 / 5 (7) Oct 25, 2013
Sounds like a good excuse to run some experiments on the ISS.
HannesAlfven
1 / 5 (9) Oct 25, 2013
Re: "Ya do realize the dispute involves plus or minus 10^minus15 ?"

It looked to me that it exceeded the error bars by 10x, btw. That should be enough to suspect that something is wrong with the theory …

Re: "I suppose those flying dinosaurs really needed that 0.02% difference to get off the ground, eh?"

Uniformitarianism -- the notion that we can simply rewind time like a tape recorder -- is a worldview. Worldviews are not scientific constructs; they are used to justify inferences and postulate hypotheses. The obvious over-simplification you make here is that our solar system and planet have not undergone dramatic changes which are difficult for us, today, to reverse-engineer. Those of us who refuse to assume the uniformitarian worldview are not crazy for avoiding the sweeping idealizations and speculations which dominate mainstream science journalism today. We simply refuse to deploy ambiguity in the data as a fudge factor to justify our own worldview.
HannesAlfven
1 / 5 (9) Oct 25, 2013
Re: "And your I assume pseudoscience link ("catastrophism" when evolution has shown it doesn't apply) doesn't show in my standard (Chrome) browser."

You seem not to realize the stereotype of pseudo-skeptics giving up on a competing idea the first opportunity they get. If you did, you'd probably have tried harder to at least pretend that you read the article which you manage to nevertheless dismiss.

Re: ""catastrophism" when evolution has shown it doesn't apply"

By the way, large-scale catastrophe is no longer a "fringe" movement in science, and there is nothing at all about acceptance of evolution which excludes catastrophe. The two ideas do not necessarily compete, and there is ample reason to suspect catastrophes based upon mass extinctions within the fossil record (come on, guys …). In fact, going out of our way to NOT consider it would be an example of a sloppy or -- more likely -- biased approach, based upon a rigid adherence to some worldview.

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