Modeling Bacterial Comets

Understanding how actin produces force by pushing rather than squeezing

Rocketing within and between human gut cells, Listeria monocytogenes—a motile, foodborne bacterium—leaves a comet-like tail of actin protein behind it and makes us sick. Scientists have long wondered how actin allows the bacterium to puncture through multiple cells and evade the human immune system. A new computational model shows how rapidly accumulating actin at the back of the bacterium produces that force.

 

In this 3-D computer simulation time series, a bead representing the Listeria monocytogenes bacterium builds actin fibers at its surface before breaking out of its shell and moving for- ward, pushed by actin fibers accumulating at the back of the bead. Reprinted from Dayel et al., In Silico Reconstitution of Actin-Based Symmetry Breaking and Motility, PLoS Biology, 7(9): e1000201 (2009), doi:10.1371/journal.pbio.1000201.“Our simulation helps us understand the basic physical properties and mechanisms by which actin can produce force,” says biophysicist Mark Dayel, PhD, a postdoctoral researcher at the University of California, Berkeley, and lead author of the paper published in the September 2009 issue of PLoS Biology. “We now have an explanation of why you get a switch from the initial pulse to smooth motion.”

 

L. monocytogenes comes from contaminated produce or milk and infects epithelial cells in the gut. Using a membrane protein called ActA, the bacterium moves by continuously building a network of actin filaments from pieces of the host’s cytoskeleton. To observe this system in action, scientists have reproduced the bacterial movement in vitro by coating tiny beads with ActA and putting them in a cell solution. Initially, actin fibers build from the surface of the bead, pushing old actin outward and forming a shell. But when the shell gets too big, it cracks and the bead bursts out, propelled forward by continual actin production. Until now, scientists thought that cracks in the outer shell spread inward and caused the shell to break. They also thought that the actin fibers stretched and then contracted behind the cell, squeezing it like a bar of soap.

 

To better understand these dynamics in detail, Dayel and his colleagues modeled the process, called “symmetry breaking.” The simulation showed that the actin shell cracks from the inside, just above the surface of the bead, where tension of the actin is greatest. When the bead bursts out, surface actin accumulates against the shell left behind and pushes the bead forward, rather than squeezing as previously believed. The model then successfully predicted what would happen to the beads in novel situations, which Dayel verified in vitro by placing new bead shapes in different conditions. Dayel says the next step is to calibrate the model so scientists can measure forces that can’t be measured in vitro. “We can extend its qualitative behavior to quantitative behavior, essentially allowing us to do virtual experiments,” Dayel says.

 

“The combination of model and experiment has made a very compelling case that the mechanisms they’re proposing are the real ones,” says Roger Kamm, PhD, professor of mechanical engineering at the Massachusetts Institute of Technology. The model is “extremely simple, yet capable of capturing some fairly complex behavior,” Kamm says.
 



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