Force transmission in migrating cells Fournier, Maxime F; Sauser, Roger; Ambrosi, Davide ...
The Journal of cell biology,
01/2010, Volume:
188, Issue:
2
Journal Article
Peer reviewed
Open access
During cell migration, forces generated by the actin cytoskeleton are transmitted through adhesion complexes to the substrate. To investigate the mechanism of force generation and transmission, we ...analyzed the relationship between actin network velocity and traction forces at the substrate in a model system of persistently migrating fish epidermal keratocytes. Front and lateral sides of the cell exhibited much stronger coupling between actin motion and traction forces than the trailing cell body. Further analysis of the traction-velocity relationship suggested that the force transmission mechanisms were different in different cell regions: at the front, traction was generated by a gripping of the actin network to the substrate, whereas at the sides and back, it was produced by the network's slipping over the substrate. Treatment with inhibitors of the actin-myosin system demonstrated that the cell body translocation could be powered by either of the two different processes, actomyosin contraction or actin assembly, with the former associated with significantly larger traction forces than the latter.
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We investigated heterocellular communication in rat mesenteric arterial strips at the cellular level using confocal microscopy. To visualize Ca
2+ changes in different cell populations, smooth muscle ...cells (SMCs) were loaded with Fluo-4 and endothelial cells (ECs) with Fura red. SMC contraction was stimulated using high K
+ solution and Phenylephrine. Depending on vasoconstrictor concentration, intracellular Ca
2+ concentration (Ca
2+
i) increased in a subpopulation of ECs 5–11
s after a Ca
2+
i rise was observed in adjacent SMCs. This time interval suggests chemical coupling between SMCs and ECs via gap junctions. As potential chemical mediators we investigated Ca
2+ or inositol 1,4,5-trisphosphate (IP
3). First, phospholipase C inhibitor U-73122 was added to prevent IP
3 production in response to the Ca
2+
i increase in SMCs. In high K
+ solution, all SMCs presented global and synchronous Ca
2+
i increase, but no Ca
2+
i variations were detected in ECs. Second, 2-aminoethoxydiphenylborate, an inhibitor of IP
3-induced Ca
2+ release, reduced the number of flashing ECs by 75
±
3% (
n
=
6). The number of flashing ECs was similarly reduced by adding the gap junction uncoupler palmitoleic acid. Thus, our results suggest a heterocellular communication through gap junctions from SMCs to ECs by diffusion, probably of IP
3.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Many experimental studies have shown that arterial smooth muscle cells respond with cytosolic calcium rises to vasoconstrictor stimulation. A low vasoconstrictor concentration gives rise to ...asynchronous spikes in the calcium concentration in a few cells (asynchronous flashing). With a greater vasoconstrictor concentration, the number of smooth muscle cells responding in this way increases (recruitment) and calcium oscillations may appear. These oscillations may eventually synchronize and generate arterial contraction and vasomotion. We show that these phenomena of recruitment and synchronization naturally emerge from a model of a population of smooth muscle cells coupled through their gap junctions. The effects of electrical, calcium, and inositol 1,4,5-trisphosphate coupling are studied. A weak calcium coupling is crucial to obtain a synchronization of calcium oscillations and the minimal required calcium permeability is deduced. Moreover, we note that an electrical coupling can generate oscillations, but also has a desynchronizing effect. Inositol 1,4,5-trisphosphate diffusion does not play an important role to achieve synchronization. Our model is validated by published in vitro experiments obtained on rat mesenteric arterial segments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress. Indeed blood flow induces intraluminal pressure variations and shear stress. An increase in pressure may ...induce a vessel contraction, a phenomenon known as the myogenic response. Many muscular vessels present vasomotion, i.e., rhythmic diameter oscillations caused by synchronous cytosolic calcium oscillations of the smooth muscle cells. Vasomotion has been shown to be modulated by pressure changes. To get a better understanding of the effect of stress and in particular pressure on vasomotion, we propose a model of a blood vessel describing the calcium dynamics in a coupled population of smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that a rise in pressure increases the calcium concentration. This may either induce or abolish vasomotion, or increase its frequency depending on the initial conditions. In our model the myogenic response is less pronounced for large arteries than for small arteries and occurs at higher values of pressure if the wall thickness is increased. Our results are in agreement with experimental observations concerning a broad range of vessels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
1 Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, Lausanne; and
2 Department of Zoology and Animal Biology, University of Geneva, Geneva, Switzerland
Submitted March 23, 2009
...; accepted in final form December 1, 2009
Vasomotion consists of cyclic arterial diameter variations induced by synchronous contractions and relaxations of smooth muscle cells. However, the arteries do not contract simultaneously on macroscopic distances, and a propagation of the contraction can be observed. In the present study, our aim was to investigate this propagation. We stimulated endothelium-denuded rat mesenteric arterial strips with phenylephrine (PE) to obtain vasomotion and observed that the contraction waves are linked to intercellular calcium waves. A velocity of 100 µm/s was measured for the two kinds of waves. To investigate the calcium wave propagation mechanisms, we used a method allowing a PE stimulation of a small area of the strip. No calcium propagation could be induced by this local stimulation when the strip was in its resting state. However, if a low PE concentration was added on the whole strip, local PE stimulations induced calcium waves, spreading over finite distances. The calcium wave velocity induced by local stimulation was identical to the velocity observed during vasomotion. This suggests that the propagation mechanisms are similar in the two cases. Using inhibitors of gap junctions and of voltage-operated calcium channels, we showed that the locally induced calcium propagation likely depends on the propagation of the smooth muscle cell depolarization. Finally, we proposed a model of the propagation mechanisms underlying these intercellular calcium waves.
conducted vasomotor response; smooth muscle cell; rat mesenteric artery
Address for reprint requests and other correspondence: D. Seppey, Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Cell Biophysics, CH-1015 Lausanne, Switzerland (e-mail: dominique.seppey{at}epfl.ch ).
In vitro, different techniques are used to study the smooth muscle cells’ calcium dynamics and contraction/relaxation mechanisms on arteries. Most experimental studies use either an isometric or an ...isobaric setup. However, in vivo, a blood vessel is neither isobaric nor isometric nor isotonic, as it is continuously submitted to intraluminal pressure variations arising from heart beat. We use a theoretical model of the smooth muscle calcium and arterial radius dynamics to determine whether results may be considerably different depending on the experimental conditions (isometric, isobaric, isotonic, or cyclic pressure variations). We show that isobaric conditions appear to be more realistic than isometric or isotonic situations, as the calcium dynamics is similar under cyclic intraluminal pressure variations (in vivo-like situation) and under a constant pressure (isobaric situation). The arterial contraction is less pronounced in isotonic than in isobaric conditions, and the vasoconstrictor sensitivity higher in isometric than isobaric or isotonic conditions, in agreement with experimental observations. Interestingly, the model predicts that isometric conditions may generate artifacts like the coexistence of multiple stable states. We have verified this model prediction experimentally using rat mesenteric arteries mounted on a wire myograph and stimulated with phenylephrine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Asynchronous and synchronous calcium oscillations occur in a variety of cells. A well-established pathway for intercellular communication is provided by gap junctions which connect adjacent cells and ...can mediate electrical and chemical coupling. Several experimental studies report that cells presenting only a transient increase when freshly dispersed may oscillate when they are coupled. Such observations suggest that the role of gap junctions is not only to coordinate calcium oscillations of adjacent cells. Gap junctions may also be important to generate oscillations. Here we illustrate the emergent properties of electrically coupled smooth muscle cells using a model that we recently proposed. A bifurcation analysis in the case of two cells reveals that synchronous and asynchronous calcium oscillations can be induced by electrical coupling. In a larger population of smooth muscle cells, electrical coupling may result in the creation of groups of cells presenting synchronous calcium oscillations. The elements of one group may be distant from each other. Moreover, our results highlight a general mechanism by which gap junctional electrical coupling can give rise to out of phase calcium oscillations in smooth muscle cells that are non-oscillating when uncoupled. All these observations remain true in the case of non-identical cells, except that the solution corresponding to synchronous calcium oscillations disappears and that the formation of groups is sensitive to the degree of heterogeneity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ