No Arabic abstract
To fulfill their killing functions, cytotoxic T lymphocytes (CTLs) need to migrate to search for their target cells in complex biological microenvironments, a key component of which is extracellular matrix (ECM). The mechanisms underlying CTLs navigation are not well understood so far. Here we use a collagen assay as a model for the ECM and analyze the migration trajectories of primary human CTLs in collagen matrices with different concentrations. We observe different migration patterns for individual T cells. Three different motility types can be distinguished: slow, fast and mixed motilities. Slow CTLs remain nearly stationary within the collagen matrix and show slightly anti-persistent motility, while the fast ones move quickly and persistent (i.e. with not too large turning angles). The dynamics of the mixed type consists of periods of slow and fast motions; both states are persistent, but they have different persistencies. The dynamics can be well described by a two-state persistent random walk model. We extract the parameters of the model by analyzing experimental data. The mean square displacements predicted by the model and those measured experimentally are in very good agreement, without any fitting parameter. Potential reasons for the observed two-state motility are discussed. T cells dig the collagen during their migration and form channels, which facilitate the movement of other CTLs in the collagen network.
Cell migration and mechanics are tightly regulated by the integrated activities of the various cytoskeletal networks. In cancer cells, cytoskeletal modulations have been implicated in the loss of tissue integrity, and acquisition of an invasive phenotype. In epithelial cancers, for example, increased expression of the cytoskeletal filament protein vimentin correlates with metastatic potential. Nonetheless, the exact mechanism whereby vimentin affects cell motility remains poorly understood. In this study, we measured the effects of vimentin expression on the mechano-elastic and migratory properties of the highly invasive breast carcinoma cell line MDA231. We demonstrate here that vimentin stiffens cells and enhances cell migration in dense cultures, but exerts little or no effect on the migration of sparsely plated cells. These results suggest that cell-cell interactions play a key role in regulating cell migration, and coordinating cell movement in dense cultures. Our findings pave the way towards understanding the relationship between cell migration and mechanics, in a biologically relevant context.
We consider population dynamics on a network of patches, each of which has a the same local dynamics, with different population scales (carrying capacities). It is reasonable to assume that if the patches are coupled by very fast migration the whole system will look like an individual patch with a large effective carrying capacity. This is called a well-mixed system. We show that, in general, it is not true that the well-mixed system has the same dynamics as each local patch. Different global dynamics can emerge from coupling, and usually must be figured out for each individual case. We give a general condition which must be satisfied for well-mixed systems to have the same dynamics as the constituent patches.
In the absence of environmental cues, a migrating cell performs an isotropic random motion. Recently, the breaking of this isotropy has been observed when cells move in the presence of asymmetric adhesive patterns. However, up to now the mechanisms at work to direct cell migration in such environments remain unknown. Here, we show that a non-adhesive surface with asymmetric micro-geometry consisting of dense arrays of tilted micro-pillars can direct cell motion. Our analysis reveals that most features of cell trajectories, including the bias, can be reproduced by a simple model of active Brownian particle in a ratchet potential, which we suggest originates from a generic elastic interaction of the cell body with the environment. The observed guiding effect, independent of adhesion, is therefore robust and could be used to direct cell migration both in vitro and in vivo.
Cells of almost all solid tissues are connected with gap junctions which permit the direct transfer of ions and small molecules, integral to regulating coordinated function in the tissue. The pancreatic islets of Langerhans are responsible for secreting the hormone insulin in response to glucose stimulation. Gap junctions are the only electrical contacts between the beta-cells in the tissue of these excitable islets. It is generally believed that they are responsible for synchrony of the membrane voltage oscillations among beta-cells, and thereby pulsatility of insulin secretion. Most attempts to understand connectivity in islets are often interpreted, bottom-up, in terms of measurements of gap junctional conductance. This does not, however explain systematic changes, such as a diminished junctional conductance in type 2 diabetes. We attempt to address this deficit via the model presented here, which is a learning theory of gap junctional adaptation derived with analogy to neural systems. Here, gap junctions are modelled as bonds in a beta-cell network, that are altered according to homeostatic rules of plasticity. Our analysis reveals that it is nearly impossible to view gap junctions as homogeneous across a tissue. A modified view that accommodates heterogeneity of junction strengths in the islet can explain why, for example, a loss of gap junction conductance in diabetes is necessary for an increase in plasma insulin levels following hyperglycemia.
Bacteria have remarkably robust cell shape control mechanisms. For example, cell diameter only varies by a few percent across a population. MreB is necessary for establishment and maintenance of rod shape although the mechanism of shape control remains unknown. We perturbed MreB in two complimentary ways to produce steady-state cell diameters over a wide range, from 790+/-30 nm to 1700+/-20 nm. To determine which properties of MreB are important for diameter control, we correlated structural characteristics of fluorescently-tagged MreB polymers with cell diameter by simultaneously analyzing 3-dimensional images of MreB and cell shape. Our results indicate that the pitch angle of MreB inversely correlates with cell diameter. Other correlations are not found to be significant. These results demonstrate that the physical properties of MreB filaments are important for shape control and support a model in which MreB dictates cell diameter and organizes cell wall growth to produce a chiral cell wall.