How Nature Controls Traffic on the Surface of Cells

Like a busy interchange, the surface of every living cell hums with activity. Proteins and lipids are constantly in motion, detecting, processing, and responding to signals from the outside world. They interact and move along a surface called the plasma membrane, a complex fluid barrier that separates the inside of a cell from everything else.

In research that will soon be published in the American Physical Society’s Physical Review X, an interdisciplinary team of scientists from Colorado State University led by Diego Krapf and Michael Tamkun sheds new light on the scaffolding that supports this membrane. Their results indicate that this spider web-like scaffolding, called the cytoskeleton, has a fractal structure. Like a cauliflower whose branches look like tiny versions of the whole vegetable, fractal structures look the same at different scales. The fractal structure of the cyctoskeleton seems to play an important role in organizing the activity on the surface of the cell.

High resolution image of the cytoskeleton filaments in a cell.
Image Credit: Diego Krapf.

Cells are the fundamental unit of life. They have been extensively studied over the last 350 years and form the basis for all of biology. But that doesn’t mean we’ve learned all of their secrets. One of the keys to understanding how cells behave is understanding how activity on the surface of a cell is organized. Proteins and lipids move around on the surface of the membrane, but research shows that they don’t always move around in the way we expect. It’s this deviation from the norm that enables them to group together and carry out biological processes.

Just as the microscope opened up the microscopic world, recent technological advances have opened up the nano-world. This means that we can study cells and how they work on a deeper level, and even capture the motion of individual proteins on the surface of a cell. In this new work, the team took extremely high resolution images of the cytoskeleton of a human cell while simultaneously tracking proteins on the cell membrane. In this way, they were able to visually explore how the cytoskeleton influences the way proteins on a cell membrane move.

To do this, the team first tagged some of the proteins on a live cell membrane with quantum dots, tiny particles that fluoresce under the right light. They imaged the cell membrane 50 times per second, and then studied how the fluorescing proteins moved along the surface. If they moved according to expectations, the proteins would wander around randomly, equally likely to go in any direction. Instead, the team found that the proteins were more likely to turn back to where they had already been, as if something was blocking the path forward.

To explore whether the cytoskeleton plays a role in limiting protein movement, as some models suggest, the team tagged the filaments that make up the cytoskeleton with another kind of light-producing marker. Then they imaged the cell membrane again, recording both the motion of the proteins and the cytoskeleton in contact with the cell membrane with very high resolution. The results show that the filaments can create temporary, fenced-in enclosures that restrict the motion of the proteins inside.

To better study the compartments created by these fences, the team imaged the cytoskeleton again, but used a fixed cell (instead of a live one) and took data for a longer period of time. Their analysis showed that over time, growing filaments randomly split existing compartments into smaller and smaller compartments.

The distribution of compartment sizes and the relationship between the perimeter of any given compartment and its area stay the same regardless of the scale you’re looking at. This is characteristic of what’s called a self-similar fractal—a structure that bears a resemblance to smaller parts of itself. A follow-up statistical analysis showed that the structure is statistically self-similar over more than three orders of magnitude. In addition, the researchers analyzed how likely the proteins are to turn back to where they’ve already been over time, and the results are also consistent with a fractal cytoskeleton.

This work shows that the cytoskeleton significantly impacts what happens on a cell membrane, and therefore how a cell functions. The fractal nature of the cytoskeleton appears to be key—playing an important role in bringing proteins together to respond to signals and carry out physiological processes.

If cell activity is anything like city traffic, there are a lot of moving parts that have the potential to bring activity to a screeching halt. Understanding how nature handles this challenge will improve our understanding of how cells work, and maybe inspire a better way to get from the suburbs into the city.

Kendra Redmond

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