Nav: Home

A traffic cop for the cell surface: Researchers illuminate a basic biological process

February 27, 2017

FORT COLLINS, COLORADO - On the surfaces of our trillions of cells is a complex crowd of molecules moving around, talking to each other, occasionally segregating themselves, and triggering basic functions ranging from pain sensation to insulin release.

The structures that organize this microscopic traffic jam are no longer invisible, thanks to Colorado State University researchers. A multidisciplinary team of single-molecule biophysicists and biochemists have shed light on a long-obscured cellular process: a mammalian cell membrane's relationship with a scaffolding underneath it, the cortical actin cytoskeleton. For the first time, the CSU team has made real-time observations of this cytoskeleton acting as a barrier that organizes proteins on the cell's surface, effectively playing traffic cop on the cell's membrane activities.

The breakthrough visualization and analysis of this most fundamental biological process - how a cell membrane interacts with its intracellular environment and controls cellular functions - was jointly achieved by the labs of Diego Krapf, associate professor of electrical and computer engineering and biomedical engineering, and Michael Tamkun, professor of biomedical sciences in the College of Veterinary Medicine and Biomedical Sciences, and of biochemistry, in the College of Natural Sciences. The researchers' study will appear in a forthcoming edition of Physical Review X, with first author Sanaz Sadegh, a Ph.D. student in Krapf's lab.

In their study, the researchers used a powerful superresolution imaging technology called photoactivated localization microscopy (PALM), which, by circumventing the natural diffraction limit of light, allows scientists to take crisp pictures and videos of biological processes at the nanoscale. Superresolution microscopy was the subject of the 2014 Nobel Prize in Chemistry.

The CSU researchers focused on the movements of potassium ion channels, a type of protein critical to cellular functions on the cell surface, and how these ion channels interact with the cortical actin cytoskeleton. The cytoskeleton is a spider-web-like network of filaments just under the cell membrane that gives the cell some of its shape and structure. Scientists had previously hypothesized that the cytoskeleton plays a critical role in helping the membrane proteins that stud the cell surface organize themselves and transmit signals to keep the cell healthy and functioning. But visually capturing this actin-protein interaction in live cells had been impossible.

"Proteins on the cell surface, like ion channels, have a lot of mass that hangs down into the cell," Tamkun explained. "It's that intracellular mass that collides with the actin network."

Using a custom-designed superresolution microscope, the researchers made movies that captured the exact moments when the ion channels collided with the actin network. What's more, they performed statistical analysis on these movements to provide evidence of the actin's key structural elements. The cortical actin network in a cell is a fractal, which means it is structurally similar at varying length scales.

"The fractal nature of the actin network explains our measurements," Sadegh said. "It leads us to question why we see so many fractals in nature. Is it an efficient way to organize functions? It's an interesting question for future studies."

The CSU researchers' analysis showed that the cell membrane proteins' random movements exhibit sophisticated patterns. Among their observations was that the proteins tended to bounce back into the places they had previously visited. For the first time, the CSU researchers offered statistical and visual evidence that this bounce-back is directly caused by the actin's fractal nature.

The chief technical challenge was achieving high-resolution images in very short time bursts, according to Krapf. "If we wait 10 seconds, the cell cytoskeleton changes, so we need to image it fast. We were employing two-second intervals, and within those seconds we needed to obtain a spatial resolution high enough to see collisions between individual membrane proteins and the actin structure."

The researchers want to understand everything about the cell membrane, because that's how the cell communicates with its outside environment, and it may hold the key to disease progression and other aspects of human health. "It's important for us to understand how the cell organizes its membrane to keep things in the places they need to be," Sadegh said. She suggested that future studies could focus on specific sites on the membrane - for example, where endocytosis takes place - and how the actin network regulates localized activity.

Colorado State University

Related Proteins Articles:

Discovering, counting, cataloguing proteins
Scientists describe a well-defined mitochondrial proteome in baker's yeast.
Interrogating proteins
Scientists from the University of Bristol have designed a new protein structure, and are using it to understand how protein structures are stabilized.
Ancient proteins studied in detail
How did protein interactions arise and how have they developed?
What can we learn from dinosaur proteins?
Researchers recently confirmed it is possible to extract proteins from 80-million-year-old dinosaur bones.
Relocation of proteins with a new nanobody tool
Researchers at the Biozentrum of the University of Basel have developed a new method by which proteins can be transported to a new location in a cell.
Proteins that can take the heat
Ancient proteins may offer clues on how to engineer proteins that can withstand the high temperatures required in industrial applications, according to new research published in the Proceedings of the National Academy of Sciences.
Designer proteins fold DNA
Florian Praetorius and Professor Hendrik Dietz of the Technical University of Munich have developed a new method that can be used to construct custom hybrid structures using DNA and proteins.
The proteins that domesticated our genomes
EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human genome.
Rare proteins collapse earlier
Some organisms are able to survive in hot springs, while others can only live at mild temperatures because their proteins aren't able to withstand such extreme heat.
How proteins reshape cell membranes
Small 'bubbles' frequently form on membranes of cells and are taken up into their interior.

Related Proteins Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...