Modeling and Simulating the Dynamics of Type IV Pili Extension of Pseudomonas aeruginosa

Abstract

Bacteria such as Pseudomonas aeruginosa use type IV pili to move across surfaces. The pili extend, attach to the surface, and then retract to move the bacteria forward. In this article, a coarse-grained model of pilus extension and attachment is developed. Simulations performed at biologically relevant conditions indicate that pilus extension is a quasistatic process such that the pili are able to relax via thermal fluctuations as it is being built and extended. Results are generated for pili with different rigidities ranging from very flexible to very stiff. It is shown that very flexible pili do not extend very far and thus would limit the bacteria to short jumps forward while stiff pili enable much greater displacements. Feasible mechanisms of attachment to the surface are also found to vary greatly between flexible and stiff pili. While it is not always the tip of flexible pili that first makes contact with the substrate, it is likely to be a part of the pili that is close to the tip. Conversely, stiff pili are much more likely to make contact with the substrate via the tip, but if not then the part of the pilus that attaches can be quite far from the tip. These results thus give insight to help resolve current discrepancies in the literature regarding pilus stiffness and the location of adhesins on pili.

Figure 1

Schematic of the coarse-grained model for pili extension. For a P. aeruginosa that is ≈500 nm in diameter, a pilus extended at the polar axis would be ≈250 nm above the substrate. To see this figure in color, go online.

Figure 2

Simulation snapshot of all four polymer lengths. Each polymer has a contour length of 2 μm. To see this figure in color, go online.

Figure 3

End-to-end distance, L_E, for each persistence length at each stage of extension indicated by the pili length, L_C. (Dashed black lines) Theoretical prediction. To see this figure in color, go online.

Figure 4

End-to-end distance for differing Péclet numbers. The four panels correspond to the four different persistence lengths simulated. To see this figure in color, go online.

Figure 5

Results for the anchor on first contact model. (Top panel) Average time that a height of −h is reached for the first time. (Middle panel) Horizontal distance from the anchor site to the attachment on the bacteria. (Bottom panel) The degree to which the polymer is fully extended on anchoring. To see this figure in color, go online.

Figure 6

Probability that the distal tip of the pili finds the substrate first. Four different persistence lengths are shown. To see this figure in color, go online.

Figure 7

Distributions for the number of times monomers other than the tip monomer find the substrate for the first time. To see this figure in color, go online.

Figure 8

Time (upper panel) and horizontal distance (lower panel) versus 1/probability of attachment for all four persistence lengths. The pili originate 50 nm above the substrate. To see this figure in color, go online.

Figure 9

Time (upper panel) and horizontal distance (lower panel) versus 1/probability of attachment for all four persistence lengths. The pili originate 250 nm above the substrate. To see this figure in color, go online.