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Register a new userCollective Motility, Mechanical Waves, and Durotaxis in Cell Clusters
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Epithelial cell clusters often move collectively on a substrate. Mechanical signals play a major role in organizing this behavior. There are a number of experimental observations in these systems which await a comprehensive explanation. These include: the internal strains are tensile even for clusters that expand by proliferation; the tractions on the substrate are often confined to the edges of the cluster; there can exist density waves within the cluster; clusters can exhibit collective durotaxis when individual cells show no effect; and for cells in an annulus there is a transition between expanding clusters with proliferation and the case where cells fill the annulus and rotate around it. We formulate a mechanical model to examine these effects. We use a molecular clutch picture which allows stalling -- inhibition of cell contraction by external forces. Stalled cells are passive from a physical point of view and the un-stalled cells are active. By attaching cells to the substrate and to each other, and taking into account contact inhibition of locomotion, we get a simple picture for many of these findings as well as predictions that could be tested. SI text/figures included, SI movies at https://rice.box.com/s/xiy3mwsfj3203lfu7pk0udfklexcgsew
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Cells coexist together in colonies or as tissues. Their behaviour is controlled by an interplay between intercellular forces and biochemical regulation. We develop a simple model of the cell cycle, the fundamental regulatory network controlling growth and division, and couple this to the physical forces arising within the cell collective. We analyse this model using both particle-based computer simulations and a continuum theory. We focus on 2D colonies confined in a channel. These develop moving growth fronts of dividing cells with quiescent cells in the interior. The profile and speed of these fronts are non-trivially related to the substrate friction and the cell cycle parameters, providing a possible approach to measure such parameters in experiments.
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Bacterial processes ranging from gene expression to motility and biofilm formation are constantly challenged by internal and external noise. While the importance of stochastic fluctuations has been appreciated for chemotaxis, it is currently believed that deterministic long-range fluid dynamical effects govern cell-cell and cell-surface scattering - the elementary events that lead to swarming and collective swimming in active suspensions and to the formation of biofilms. Here, we report the first direct measurements of the bacterial flow field generated by individual swimming Escherichia coli both far from and near to a solid surface. These experiments allowed us to examine the relative importance of fluid dynamics and rotational diffusion for bacteria. For cell-cell interactions it is shown that thermal and intrinsic stochasticity drown the effects of long-range fluid dynamics, implying that physical interactions between bacteria are determined by steric collisions and near-field lubrication forces. This dominance of short-range forces closely links collective motion in bacterial suspensions to self-organization in driven granular systems, assemblages of biofilaments, and animal flocks. For the scattering of bacteria with surfaces, long-range fluid dynamical interactions are also shown to be negligible before collisions; however, once the bacterium swims along the surface within a few microns after an aligning collision, hydrodynamic effects can contribute to the experimentally observed, long residence times. As these results are based on purely mechanical properties, they apply to a wide range of microorganisms.
Motile biological cells in tissue often display the phenomenon of durotaxis, i.e. they tend to move towards stiffer parts of substrate tissue. The mechanism for this behavior is not completely understood. We consider simplified models for durotaxis based on the classic persistent random walker scheme. We show that even a one-dimensional model of this type sheds interesting light on the classes of behavior cells might exhibit. Our results strongly indicate that cells must be able to sense the gradient of stiffness in order to show the effects observed in experiment. This is in contrast to the claims in recent publications that it is sufficient for cells to be more persistent in their motion on stiff substrates to show durotaxis: i.e., if would be enough to sense the value of the stiffness. We show that these cases give rise to extremely inefficient transport towards stiff regions. Gradient sensing is almost certainly the selected behavior.
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