scholarly journals Environmentally dependent and independent control of cell shape determination by Rho GTPase regulators in melanoma

2021 ◽  
Author(s):  
Lucas G Dent ◽  
Nathan Curry ◽  
Hugh Sparks ◽  
Vicky Bousgouni ◽  
Vincent Maioli ◽  
...  

In order to invade 3D tissues, cancer cells dynamically change cell morphology in response to geometric and mechanical cues in the environment. But how cells determine their shape in 3D versus 2D environments is poorly understood. Studying 2D versus 3D single cell shape determination has historically been technically difficult due to the lack of methodologies to directly compare the two environments. We developed an approach to study cell shape in 2D versus 3D by measuring cell shape at different depths in collagen using stage-scanning oblique plane microscopy (ssOPM). We find characteristic shape changes occur in melanoma cells depending on whether a cell is attached to a 2D surface or 3D environment, and that these changes can be modulated by Rho GTPase regulatory proteins. Our data suggest that regulation of cell protrusivity undergoes a switch of control between different Rho GTPase regulators depending on the physical microenvironment.

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 679-691 ◽  
Author(s):  
M.M. Myat ◽  
D.J. Andrew

During Drosophila development, the salivary primordia are internalized to form the salivary gland tubes. By analyzing immuno-stained histological sections and scanning electron micrographs of multiple stages of salivary gland development, we show that internalization occurs in a defined series of steps, involves coordinated cell shape changes and begins with the dorsal-posterior cells of the primordia. The ordered pattern of internalization is critical for the final shape of the salivary gland. In embryos mutant for huckebein (hkb), which encodes a transcription factor, or faint sausage (fas), which encodes a cell adhesion molecule, internalization begins in the center of the primordia, and completely aberrant tubes are formed. The sequential expression of hkb in selected cells of the primordia presages the sequence of cell movements. We propose that hkb dictates the initial site of internalization, the order in which invagination progresses and, consequently, the final shape of the organ. We propose that fas is required for hkb-dependent signaling events that coordinate internalization.


Author(s):  
Jun Matsuda ◽  
Kana Asano-Matsuda ◽  
Thomas Kitzler ◽  
Tomoko Takano

2011 ◽  
Vol 94 (2) ◽  
pp. 133-148 ◽  
Author(s):  
Kimberley F. Tolias ◽  
Joseph G. Duman ◽  
Kyongmi Um

Soft Matter ◽  
2019 ◽  
Vol 15 (42) ◽  
pp. 8425-8436 ◽  
Author(s):  
Yashar Bashirzadeh ◽  
Allen P. Liu

The cytoskeleton of a cell controls all the aspects of cell shape changes. Such conserved and effective control over the mechanics of the cell makes the cytoskeletal components great candidates for bottom-up synthetic biology studies.


2019 ◽  
Author(s):  
Elisabeth G. Rens ◽  
Leah Edelstein-Keshet

AbstractSingle and collective cell dynamics, cell shape changes, and cell migration can be conveniently represented by the Cellular Potts Model, a computational platform based on minimization of a Hamiltonian while permitting stochastic fluctuations. Using the fact that a force field is easily derived from a scalar energy (F = −∇H), we develop a simple algorithm to associate effective forces with cell shapes in the CPM. We display the predicted forces for single cells of various shapes and sizes (relative to cell rest-area and cell rest-perimeter). While CPM forces are specified directly from the Hamiltonian on the cell perimeter, we infer internal forces using interpolation, and refine the results with smoothing. Predicted forces compare favorably with experimentally measured cellular traction forces. We show that a CPM model with internal signaling (such as Rho-GTPase-related contractility) can be associated with retraction-protrusion forces that accompany cell shape changes and migration. We adapt the computations to multicellular systems, showing, for example, the forces that a pair of swirling cells exert on one another, demonstrating that our algorithm works equally well for interacting cells. Finally, we show forces associated with the dynamics of classic cell-sorting experiments in larger clusters of model cells.Author summaryCells exert forces on their surroundings and on one another. In simulations of cell shape using the Cellular Potts Model (CPM), the dynamics of deforming cell shapes is traditionally represented by an energy-minimization method. We use this CPM energy, the Hamiltonian, to derive and visualize the corresponding forces exerted by the cells. We use the fact that force is the negative gradient of energy to assign forces to the CPM cell edges, and then extend the results to interior forces by interpolation. We show that this method works for single as well as multiple interacting model cells, both static and motile. Finally, we show favorable comparison between predicted forces and real forces measured experimentally.


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