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.