Navigation Links
Computer simulations yield clues to how cells interact with surroundings
Date:3/22/2013

Your cells are social butterflies. They constantly interact with their surroundings, taking in cues on when to divide and where to anchor themselves, among other critical tasks.

This networking is driven in part by proteins called integrin, which reside in a cell's outer plasma membrane. Their job is to convert mechanical forces from outside the cell into internal chemical signals that tell the cell what to do. That is, when they work properly. When they misfire, integrins can cause diseases such as atherosclerosis and several types of cancer.

Despite their importancegood and badscientists don't exactly know how integrins work. That's because it's very difficult to experimentally observe the protein's molecular machinery in action. Scientists have yet to obtain the entire crystal structure of integrin within the plasma membrane, which is a go-to way to study a protein's function. Roadblocks like this have ensured that integrins remain a puzzle despite years of research.

But what if there was another way to study integrin? One that doesn't rely on experimental methods? Now there is, thanks to a computer model of integrin developed by Berkeley Lab researchers. Like its biological counterpart, the virtual integrin snippet is about twenty nanometers long. It also responds to changes in energy and other stimuli just as integrins do in real life. The result is a new way to explore how the protein connects a cell's inner and outer environments.

"We can now run computer simulations that reveal how integrins in the plasma membrane translate external mechanical cues to chemical signals within the cell," says Mohammad Mofrad, a faculty scientist in Berkeley Lab's Physical Biosciences Division and associate professor of Bioengineering and Mechanical Engineering at UC Berkeley. He conducted the research with his graduate student Mehrdad Mehrbod.

They report their research in a recent issue of PLOS Computational Biology: http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002948

Their "molecular dynamics" model is the latest example of computational biology, in which scientists use computers to analyze biological phenomena for insights that may not be available via experiment. As you'd expect from a model that accounts for the activities of half a million atoms at once, the integrin model takes a lot of computing horsepower to pull off. Some of its simulations require 48 hours of run time on 600 parallel processors at the U.S. Department of Energy's (DOE) National Energy Research Scientific Computing Center (NERSC), which is located at Berkeley Lab.

The model is already shedding light on what makes integrin tick, such as how they "know" to respond to more force with greater numbers. When activated by an external force, integrins cluster together on a cell's surface and join other proteins to form structures called focal adhesions. These adhesions recruit more integrins when they're subjected to higher forces. As the model indicates, this ability to pull in more integrins on demand may be due to the fact that a subunit of integrin is connected to actin filaments, which form a cell's skeleton.

"We found that if actin filaments sustain more forces, they automatically bring more integrins together, forming a larger cluster," says Mehrbod.

The model may also help answer a longstanding question: Do integrins interact with each other immediately after they're activated? Or do they not interact with each other at all, even as they cluster together?

To find out, the scientists ran simulations that explored whether it's physically possible for integrins to interact when they're embedded in the plasma membrane. They found that interactions are likely to occur only between one compartment of integrin called the β-subunit.

They also discovered an interesting pattern in which integrins fluctuate. Two integrin sections, one that spans the cell membrane and one that protrudes from the cell, are connected by a hinge-like region. This hinge swings about when the protein is forced to vibrate as a result of frequent kicks from other molecules around it, such as water molecules, lipids, and ions.

These computationally obtained insights could guide new experiments designed to uncover how integrins do their job.

"Our research sets up an avenue for future studies by offering a hypothesis that relates integrin activation and clustering," says Mofrad.


'/>"/>

Contact: Dan Krotz
dakrotz@lbl.gov
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert

Related biology news :

1. Computer model may help athletes and soldiers avoid brain damage and concussions
2. Computer modeling reveals how surprisingly potent hepatitis C drug works
3. New supercomputer to aid genomics research
4. New supercomputer coming to EMSL this summer, supplied by Atipa Technologies
5. Virginia Tech computer scientists develop new way to study molecular networks
6. Iowa State computer, electrical engineers working to help biologists cope with big data
7. How computers push on the molecules they simulate
8. Total donates high-speed computer cluster to UH
9. A better thought-controlled computer cursor
10. Computers taught to ID regulating gene sequences
11. Computer simulations for multiscale systems can be faster, better, more reliable
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/5/2016)... 5, 2016 http://www.researchandmarkets.com/research/5kvw8m/global_facial ... "Global Facial Recognition Market 2016-2020" ... http://www.researchandmarkets.com/research/5kvw8m/global_facial ) has announced the addition of ... report to their offering. --> ... has announced the addition of the ...
(Date:2/3/2016)... , February 3, 2016 ... market research report "Automated Fingerprint Identification System Market by ... Search), Application (Banking & Finance, Government, Healthcare, and Transportation) ... MarketsandMarkets, the market is expected to be worth USD ... 21.0% between 2015 and 2020. The transformation and technology ...
(Date:2/2/2016)... YORK , Feb. 2, 2016 /PRNewswire/ ... facilities are primarily focused on medical screening ... measure point-of-care parameters. Wearable devices that facilitate ... user,s freedom of movement are being bolstered ... for human biomedical signal acquisition coupled with ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... 2016 ASAE is introducing a hybrid membership ... (AMC) the option of joining or renewing through an ... by staff size, every employee in any size association ... reap all available member benefits.   John ... membership options will allow organizations of any size and ...
(Date:2/10/2016)... -- Allergan plc (NYSE: AGN ) a leading global ... Allergan,s CEO and President, will be featured as the ... RBC Capital Markets Healthcare Conference on Tuesday, February 23, ... Palace Hotel in New York, NY ... be accessed on Allergan,s Investor Relations web site at ...
(Date:2/10/2016)... ... February 10, 2016 , ... HOLLOWAY AMERICA, a leading custom ... Rocky Mountain Chapter 21st Annual Vendor Exhibition on Thursday, February 18, 2016. The ... for its annual event, which will run from 3:00 p.m. - 8:30 p.m. ...
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... ... Testing (PROMPT), a research registry built on the secure online PatientCrossroads platform, has ... More than 1,600 participants have joined the PROMPT study, which seeks to advance ...
Breaking Biology Technology: