How do cells generate forces for intracellular transport and whole-cell migration? How are objects within the cell positioned? The cell must address these micron-scale issues using nanometer-scale biochemical components.
Bacterial chromosome segregation
When a cell divides, it must reliably replicate its DNA and pass the replicated chromosomes and plasmids along to its daughter cell. Although this process is fundamental to all cells, the force-generating mechanisms underlying chromosome segregation are not well-understood. At a glance, the mechanism of chromosome segregation in Caulobacter crescentus is counterintuitive. Once DNA replication begins at one cell pole, a segment of the replicated chromosome (parS) is coated with the ParB protein. Meanwhile, a structure of actin-like ParA protein grows from the opposite cell pole until contacting the ParB-decorated chromosome. ParB binds to ParA and begins to disassemble it. As ParA retracts by depolymerization, it pulls the ParB-coated chromosome across the cell. No other components are known to be necessary for this process. How can ParA pull the chromosome at the very points that seem to be disintegrating?
In our paper with Ned Wingreen and Zemer Gitai at Princeton, we explain that self-diffusiophoresis is sufficient for robust chromosome pulling. This mechanism for chromosome motility relies on self-generated and self-sustaining concentration gradients. Since the ParB attached to the chromosome depolymerizes ParA, it creates a concentration gradient of ParA; since it ParB is attracted to ParA, it moves up the gradient towards higher ParA concentrations. This steady-state process pulls the DNA across the cell, as can be seen in our Brownian dynamics simulations.
Some experimental images of this process in C. crescentus and Vibrio cholerae can be seen in papers by Shebelut et al. (2010) PNAS 107:14194 and Fogel and Waldor (2006) Genes Dev. 20:3269, respectively.
Actin-polymerization-driven motility
During actin-based motility, a cell polymerizes actin protein into a dense, branched network behind the leading edge of the cell membrane. This protein network is involved in creating membrane protrusions and assisting in cellular motility. A model system for actin-based motility is Listeria monocytogenes, which infects larger cells and hijacks their actin-polymerization machinery. In doing so, it develops a dense actin network behind its rear surface, which propels it forward. As it moves, the actin network continues to grow behind the bacterium, so that propulsion is maintained in steady-state. This process has previously been studied by Kun-Chun Lee and Andrea Liu. In their two papers, they propose that self-diffusiophoresis, relying on a bacterium-generated actin concentration gradient that drives the bacteria forward by repulsive interactions, can explain the mechanism of propulsion and force-velocity relation of actin-based motility.
One remaining question is whether the mechanism of motility can be sustained in the presence of proteins that bind actin to the bacterial surface. Recently, we have found that cellular motility is not disrupted by the presence of local attractive interactions between the bacterium and actin, and is thus insensitive to the inclusion of proteins that bind the actin network to the bacterium. More information can be found in our paper
Theoretical model for self-propulsion and self-organizing interactions
See our paper.
References
- EJ Banigan, MA Gelbart, Z Gitai, NS Wingreen, and AJ Liu (2011) Filament depolymerization can explain chromosome pulling during bacterial mitosis. PLoS Comput. Biol. 7: e1002145.
- EJ Banigan, KC Lee, and AJ Liu (2013) Control of actin-based motility through localized actin binding. Phys. Biol. 10: 066004.
- EJ Banigan and JF Marko (2016) Self-propulsion and interactions of catalytic particles in a chemically active medium. Phys. Rev. E 93: 012611.