Using data supplied by researchers at the Max Planck Institute, Univ. of Illinois postdoctoral researcher Elijah Roberts and chemistry professor Zaida Luthey-Schulten built a computer model of a bacterial cell that accurately simulates the behavior of actual cells. Credit: L. Brian Stauffer
Researchers have built a computer model of the crowded interior
of a bacterial cell that—in a test of its response to sugar in its environment—accurately
simulates the behavior of living cells.
The new “in silico
cells” are the result of a collaboration between experimental scientists at the
Max Planck Institute of Biology in Germany
and theoretical scientists at the Univ.
of Illinois using the newest GPU (graphics processing unit) computing
Their study appears in PLoS
“This is the first time that we’re modeling entire cells
with the complete contents of the cellular cytoplasm represented,” said Illinois postdoctoral
researcher and lead author Elijah Roberts. “We’re looking at the influence of
the whole cellular architecture instead of modeling just a portion of the cell,
as people have done previously.”
of Illinois chemistry
professor Zaida Luthey-Schulten, who led the research, had done molecular
dynamics simulations of individual molecules or groups of molecules involved in
information processing, but never of a system as large and complex as the
interior of an entire cell.
Then in 2006 she saw a paper by Wolfgang Baumeister and his
colleagues at Max Planck that located every one of a bacterium’s ribosomes, its
protein-building machines, inside the cell.
That image spurred Luthey-Schulten to think about modeling
an entire cell, and she asked Baumeister and his colleague Julio Ortiz if they
would repeat the study in Escherichia
coli (E. coli), a bacterium that
has been the subject of numerous molecular studies.
Once the new ribosome data were available, Roberts looked to
other studies that described the size distribution of the rest of the molecules
that take up space in the cell. By adding these to the ribosome data, he
developed a three-dimensional model that showed the degree of “molecular
crowding” in a typical E. coli cell.
Luthey-Schulten was amazed at how little “space” remained
inside the cell, she said.
“I think, like everybody else, my perception of the cell up
until Wolfgang and Julio’s 2006 article had always been that it’s a pretty big
sack of water where a lot of chemical reactions occur,” she said.
“But in fact there are a lot of obstacles in the cell, and
that is going to affect how individual molecules move around and it’s going to
affect the reactions that occur.”
Other researchers have begun studying the effects of
molecular crowding on cellular processes, but never at the scale of an entire
Those studying live cells can—by conducting fluorescence
experiments—discover variations in the copy number of a particular protein in a
population of cells. But they are less able to observe the microscopic details
that give rise to such differences between genetically identical cells.
Well-designed computer simulations of whole cells can track every reaction
within the cells while also accounting for the influence of molecular crowding
and other variations between cells, Luthey-Schulten said.
For example, by running simulations on models of two E. coli strains, the researchers were
able to see that “bacterial cell architecture does indeed affect the reactions
that occur within the cells,” Luthey-Schulten said. When sugar was present in
its environment, a longer, narrower E.
coli strain was able to ramp up production of a sugar-transporter protein
much more quickly than a bigger strain, the researchers found. That difference
had a lot to do with the distribution of molecules in each cell type, Roberts
The computer simulation also showed how molecular crowding
influences the behavior of a molecule that, when it binds to DNA, shuts down production
of the sugar-transporter protein. Even when it wasn’t bound to DNA, this
repressor remained close to the binding site because other molecules in the
cell blocked its escape. These intracellular obstacles reduced its ability to
The new model is only a first step toward an accurate
simulation of a whole working cell, the researchers said. The development of
better models will rely on the work of those conducting research on actual
cells. Their data provide the framework for improving computer models,
Luthey-Schulten said, and offer a real-world test of the in silico cells’ ability to recreate the behavior of living cells.
Future studies will further develop the E. coli models and will focus on methane-generating archaeal