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Bacterial pathogens are often classified by their toxicity and invasiveness. The invasiveness of a given bacterium is determined by how capable the bacterium is at invading a broad range of tissues in its host. Of mammalian pathogens, some of the most invasive come from a group of bacteria known as the spirochetes, which cause diseases, such as syphilis, Lyme disease, relapsing fever and leptospirosis. Most of the spirochetes are characterized by their distinct shapes and unique motility. They are long, thin bacteria that can be shaped like flat-waves, helices, or have more irregular morphologies. Like many other bacteria, the spirochetes use long, helical appendages known as flagella to move; however, the spirochetes enclose their flagella in the periplasm, the narrow space between the inner and outer membranes. Rotation of the flagella in the periplasm causes the entire cell body to rotate and/or undulate. These deformations of the bacterium produce the force that drives the motility of these organisms, and it is this unique motility that likely allows these bacteria to be highly invasive in mammals. This review will describe the current state of knowledge on the motility and biophysics of these organisms and provide evidence on how this knowledge can inform our understanding of spirochetal diseases. [ABSTRACT FROM AUTHOR]

When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the ''wound.'' In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism). In adult tissue, though, cells apparently crawl to close wounds. At the single cell level, this crawling is driven by the dynamics of the cell's actin cytoskeleton, which is regulated by a complex biochemical network, and cell signaling has been proposed to play a significant role in directing cells to move into the denuded area. However, wounds made in monolayers of Madin-Darby canine kidney (MDCK) cells still close even when a row of cells is deactivated at the periphery of the wound, and recent experiments show complex, highly-correlated cellular motions that extend tens of cell lengths away from the boundary. These experiments suggest a dominant role for mechanics in wound healing. Here we present a biophysical description of the collective migration of epithelial cells during wound healing based on the basic motility of single cells and cell-cell interactions. This model quantitatively captures the dynamics of wound closure and reproduces the complex cellular flows that are observed. These results suggest that wound healing is predominantly a mechanical process that is modified, but not produced, by cell-cell signaling. [ABSTRACT FROM AUTHOR]

Abstract: Eukaryotic cell crawling is a highly complex biophysical and biochemical process, where deformation and motion of a cell are driven by internal, biochemical regulation of a poroelastic cytoskeleton. One challenge to built quantitative models that describe crawling cells is solving the reaction–diffusion–advection dynamics for the biochemical and cytoskeletal components of the cell inside its moving and deforming geometry. Here we develop an algorithm that uses the level set method to move the cell boundary and uses information stored in the distance map to construct a finite volume representation of the cell. Our method preserves Cartesian connectivity of nodes in the finite volume representation while resolving the distorted cell geometry. Derivatives approximated using a Taylor series expansion at finite volume interfaces lead to second order accuracy even on highly distorted quadrilateral elements. A modified, Laplacian-based interpolation scheme is developed that conserves mass while interpolating values onto nodes that join the cell interior as the boundary moves. An implicit time stepping algorithm is used to maintain stability. We use the algorithm to simulate two simple models for cellular crawling. The first model uses depolymerization of the cytoskeleton to drive cell motility and suggests that the shape of a steady crawling cell is strongly dependent on the adhesion between the cell and the substrate. In the second model, we use a model for chemical signalling during chemotaxis to determine the shape of a crawling cell in a constant gradient and to show cellular response upon gradient reversal. [ABSTRACT FROM AUTHOR]

The filaments of spirochete periplasmic flagella (PFs) have a unique structure and protein composition. In most spirochetes, the PFs consist of a core of at least three related proteins (FlaB1, FlaB2, and FlaB3) and a sheath of FlaA protein. The functions of these filament proteins remain unknown. In this study, we used a multidisciplinary approach to examine the role of these proteins in determining the composition, shape, and stiffness of the PFs and how these proteins impact motility by using the spirochete Brachyspira (formerly Treponema, Serpulina) hyodysenteriae as a genetic model. A series of double mutants lacking combinations of these PF proteins was constructed and analyzed. The results show the following. First, the diameters of PFs are primarily determined by the sheath protein FlaA, and that FlaA can form a sheath in the absence of an intact PF core. Although the sheath is important to the PF structure and motility, it is not essential. Second, the three core proteins play unequal roles in determining PF structure and swimming speed. The functions of the core proteins FlaB1 and FlaB2 overlap such that either one of these proteins is essential for the spirochete to maintain the intact PF structure and for cell motility. Finally, linear elasticity theory indicates that flagellar stiffness directly affects the spirochete's swimming speed. [ABSTRACT FROM AUTHOR]