Researchers develop computer model to study cell membrane dynamics

Apr 08, 2008

A cell constantly remodels its fluid membranes to carry out critical tasks, such as recognizing other cells, getting nutrients or sorting proteins. Because membranes are fluid and intrinsically disordered, investigating these and other life-sustaining processes in detail has always been difficult. But a computer model developed by Markus Deserno, associate professor of physics at Carnegie Mellon University, provides a new approach by allowing him to simulate and observe membrane dynamics at a relatively large scale -- hundreds of nanometers. It is at this scale that many critical membrane-mediated processes take place.

Deserno will describe the application of this model to the biophysical problem of vesicle creation on Tuesday, April 8 at the 235th national meeting of the American Chemical Society in New Orleans.

“Our model is coarse-grained,” Deserno said. “You can think of it as an impressionist painting. At a distance, everything looks good. You can see water lilies or ballerinas. But up close, all the details are gone; you just see blotches of color. We’re interested in what’s happening with the water lilies, not the blotches of color,” he added.

With this coarse-grained model, Deserno can accurately capture important large-scale characteristics, like how the membrane bends and curves, which allows him to ask questions that are beyond the atomic resolution but less than the size of an entire cell. His model is also versatile as he can add proteins of interest to the lipid membrane and observe how they interact.

Using this computer model, Deserno and colleagues at the Max Plank Institute for Polymer Research in Mainz, Germany, recently revealed a purely physical mechanism that enables vesiculation — the process by which cell membranes curve around proteins or other cellular cargo to form “vesicles.” Without this generic ability to curve its protein-studded membranes and bud off cargo shuttles, a cell couldn’t survive.

“Ultimately, understanding the dynamics of vesiculation is key to advancing the design of anti-viral therapies or understanding how protein processing goes awry within a cell and leads to disease,” Deserno said.

Deserno and his team created a computer simulation of a cell membrane with a lipid bilayer — a soap-like film made of 50,000 individual lipids molecules — and studded it with 36 evenly spaced and contact lens-shaped disks representing remodeling proteins, which are involved in vesiculation. Then he set the simulation to allow the fluid membrane to fluctuate as it normally would. During the simulation, the artificial membrane began curving in places. In creating curved membrane structures, each disk bent the membrane slightly. This local curvature spread around a disk like a little “halo.” When two disks approached one another, the overlapping halos led to an indirect interaction. Thus, while there was no explicit interaction between the disks, these objects indirectly attracted each other via the membrane, Deserno’s group found.

“With this work, we provide solid support for a mechanism that has been gaining in popularity recently,” Deserno said. “To date, no one has demonstrated at the biophysical level exactly what most people have come to accept as evident — that remodeling proteins can indeed aggregate and facilitate vesiculation based on their curvature imprint alone. Our simulations show that proteins need not interact directly to drive this critical process.”

Understanding how vesiculation physically operates should make it easier in the long run to rationally design and deliver drugs to individual cells, according to Deserno. “This is the biggest practical value of our research. Now that we have a proposed mechanism, we can subject it to well-posed questions, such as why certain proteins are always present during vesiculation.”

In addition to investigating the process of membrane mediated interactions in computer simulations, Deserno, together with colleagues Jemal Guven at the Universidad Nacional Autónoma de México and Martin Müller at the École Normale Supérieure in Paris, has developed powerful theoretical tools to study the transport of stresses and forces through curved membranes.

Source: Carnegie Mellon University

Explore further: Meteorite that doomed dinosaurs remade forests

add to favorites email to friend print save as pdf

Related Stories

Final pieces to the circadian clock puzzle found

1 hour ago

Researchers at the UNC School of Medicine have discovered how two genes – Period and Cryptochrome – keep the circadian clocks in all human cells in time and in proper rhythm with the 24-hour day, as well ...

A spray-on light show on four wheels: Darkside Scientific

2 hours ago

Darkside Scientific recently drew a lot of gazes its way in its video release of a car treated to the company's electroluminescent paint called LumiLor. Electroluminescence (EL) is a characteristic of a material ...

Measuring modified protein structures

5 hours ago

Swiss researchers have developed a new approach to measure proteins with structures that change. This could enable new diagnostic tools for the early recognition of neurodegenerative diseases to be developed.

Recommended for you

Iberian pig genome remains unchanged after five centuries

22 minutes ago

A team of Spanish researchers have obtained the first partial genome sequence of an ancient pig. Extracted from a sixteenth century pig found at the site of the Montsoriu Castle in Girona, the data obtained indicates that ...

Spy on penguin families for science

2 hours ago

Penguin Watch, which launches on 17 September 2014, is a project led by Oxford University scientists that gives citizen scientists access to around 200,000 images of penguins taken by remote cameras monitoring ...

User comments : 0