Cell Morphodynamics Research Articles

Effects of various kinetic rates of FtsZ filaments on bacterial cytokinesis.

Cell morphodynamics during bacterial cytokinesis are theoretically explored by a combination of phase field model for rod-shaped cells and a kinetic description for FtsZ ring maintenance. The division times and cell shapes have been generally decided by the competition between the constriction forces generated by FtsZ rings and the curvature elastic energy for cells. The dependences of cell morphodynamics during bacterial cytokinesis on various kinetic rates of FtsZ filaments are focused in the present study. It is found that the obtained results with the experimental parameters are well comparable to the observed results physiologically. Likewise, the quasi-steady states for FtsZ rings are found to be well consistent with the theoretical results derived from the kinetic description of FtsZ rings. In addition, morphological phase diagram is presented as functions of the membrane associate rate for both short FtsZ filaments and free FtsZ monomers, and the depolymerization rate of GDP-bound FtsZ monomers at the tip of filaments within the ring. Our results would provide a better understanding of the details of in vivo kinetics, including the kinetic rates within FtsZ rings.

Coupling FtsZ filaments and morphodynamics during bacterial cell division

Cell morphodynamics during bacterial cell division is extensively investigated by a combination of a phase field model for rod-shaped cells and a kinetic description for FtsZ ring maintenance.

SH3BP1, an Exocyst-Associated RhoGAP, Inactivates Rac1 at the Front to Drive Cell Motility

The coordination of the several pathways involved in cell motility is poorly understood. Here, we identify SH3BP1, belonging to the RhoGAP family, as a partner of the exocyst complex and establish a physical and functional link between two motility-driving pathways, the Ral/exocyst and Rac signaling pathways. We show that SH3BP1 localizes together with the exocyst to the leading edge of motile cells and that SH3BP1 regulates cell migration via its GAP activity upon Rac1. SH3BP1 loss of function induces abnormally high Rac1 activity at the front, as visualized by in vivo biosensors, and disorganized and instable protrusions, as revealed by cell morphodynamics analysis. Consistently, constitutively active Rac1 mimics the phenotype of SH3BP1 depletion: slow migration and aberrant cell morphodynamics. Our finding that SH3BP1 downregulates Rac1 at the motile-cell front indicates that Rac1 inactivation in this location, as well as its activation by GEF proteins, is a fundamental requirement for cell motility.

Abnormal actomyosin assembly in proliferating and differentiating myoblasts upon expression of a cytosolic DMPK isoform

DMPK, the product of the mutated gene in myotonic dystrophy type 1, belongs to the subfamily of Rho-associated serine–threonine protein kinases, whose members play a role in actin-based cell morphodynamics. Not much is known about the physiological role of differentially localized individual DMPK splice isoforms. We report here that prominent stellar-shaped stress fibers are formed during early and late steps of differentiation in DMPK-deficient myoblast–myotubes upon complementation with the short cytosolic DMPK E isoform. Expression of DMPK E led to an increased phosphorylation status of MLC2. We found no such effects with vectors that encode a mutant DMPK E which was rendered enzymatically inactive or any of the long C-terminally anchored DMPK isoforms. Presence of stellar structures appears associated with changes in cell shape and motility and a delay in myogenesis. Our data strongly suggest that cytosolic DMPK participates in remodeling of the actomyosin cytoskeleton in developing skeletal muscle cells.

Computational model for cell morphodynamics.

We develop a computational model, based on the phase-field method, for cell morphodynamics and apply it to fish keratocytes. Our model incorporates the membrane bending force and the surface tension and enforces a constant area. Furthermore, it implements a cross-linked actin filament field and an actin bundle field that are responsible for the protrusion and retraction forces, respectively. We show that our model predicts steady state cell shapes with a wide range of aspect ratios, depending on system parameters. Furthermore, we find that the dependence of the cell speed on this aspect ratio matches experimentally observed data.

Cells Segmentation From 3-D Confocal Images of Early Zebrafish Embryogenesis

We designed a strategy for extracting the shapes of cell membranes and nuclei from time lapse confocal images taken throughout early zebrafish embryogenesis using a partial-differential-equation-based segmentation. This segmentation step is a prerequisite for an accurate quantitative analysis of cell morphodynamics during embryogenesis and it is the basis for an integrated understanding of biological processes. The segmentation of embryonic cells requires live zebrafish embryos fluorescently labeled to highlight sub-cellular structures and designing specific algorithms by adapting classical methods to image features. Our strategy includes the following steps: the signal-to-noise ratio is first improved by an edge-preserving filtering, then the cell shape is reconstructed applying a fully automated algorithm based on a generalized version of the Subjective Surfaces technique. Finally we present a procedure for the algorithm validation either from the accuracy and the robustness perspective.

Molecular-scale Topographic Cues Induce the Orientation and Directional Movement of Fibroblasts on Two-dimensional Collagen Surfaces

Collagen fibres within the extracellular matrix lend tensile strength to tissues and form a functional scaffold for cells. Cells can move directionally along the axis of fibrous structures, in a process important in wound healing and cell migration. The precise nature of the structural cues within the collagen fibrils that can direct cell movement are not known. We have investigated the structural features of collagen that are required for directional motility of mouse dermal fibroblasts, by analysing cell movement on two-dimensional collagen surfaces. The surfaces were prepared with aligned fibrils of collagen type I, oriented in a predefined direction. These collagen-coated surfaces were generated with or without the characteristic 67 nm D-periodic banding. Quantitative analysis of cell morphodynamics showed a strong correlation of cell elongation and motional directionality with the orientation of D-periodic collagen microfibrils. Neither directed motility, nor cell body alignment, was observed on aligned collagen lacking D-periodicity, or on D-periodic collagen in the presence of peptide containing an RGD motif. The directional motility of fibroblast cells on aligned collagen type I fibrils cannot be attributed to contact guidance, but requires additional structural information. This allows us to postulate a physiological function for the 67 nm periodicity.