Anisotropy links cell shapes to tissue flow during convergent extension

Within developing embryos, tissues flow and reorganize dramatically on timescales as short as minutes. This includes epithelial tissues, which often narrow and elongate in convergent extension movements due to anisotropies in external forces or in internal cell-generated forces. However, the mechanisms that allow or prevent tissue reorganization, especially in the presence of strongly anisotropic forces, remain unclear. We study this question in the converging and extending Drosophila germband epithelium, which displays planar polarized myosin II and experiences anisotropic forces from neighboring tissues, and we show that in contrast to isotropic tissues, cell shape alone is not sufficient to predict the onset of rapid cell rearrangement. From theoretical considerations and vertex model simulations, we predict that in anisotropic tissues two experimentally accessible metrics of cell patterns, the cell shape index and a cell alignment index, are required to determine whether an anisotropic tissue is in a solid-like or fluid-like state. We show that changes in cell shape and alignment over time in the Drosophila germband predict the onset of rapid cell rearrangement in both wild-type and snail twist mutant embryos, where our theoretical prediction is further improved when we also account for cell packing disorder. These findings suggest that convergent extension is associated with a transition to more fluid-like tissue behavior, which may help accommodate tissue shape changes during rapid developmental events

Molecular basis of filamin a-filGAP interaction and its impairment in congenital disorders associated with filamin a mutations

Peer reviewe

Mechanical control of neural plate folding by apical domain alteration

Abstract Vertebrate neural tube closure is associated with complex changes in cell shape and behavior, however, the relative contribution of these processes to tissue folding is not well understood. At the onset of Xenopus neural tube folding, we observed alternation of apically constricted and apically expanded cells. This apical domain heterogeneity was accompanied by biased cell orientation along the anteroposterior axis, especially at neural plate hinges, and required planar cell polarity signaling. Vertex models suggested that dispersed isotropically constricting cells can cause the elongation of adjacent cells. Consistently, in ectoderm, cell-autonomous apical constriction was accompanied by neighbor expansion. Thus, a subset of isotropically constricting cells may initiate neural plate bending, whereas a ‘tug-of-war’ contest between the force-generating and responding cells reduces its shrinking along the body axis. This mechanism is an alternative to anisotropic shrinking of cell junctions that are perpendicular to the body axis. We propose that apical domain changes reflect planar polarity-dependent mechanical forces operating during neural folding

The cell as a material This review comes from a themed issue on Cell structure and dynamics Edited by Daniel P Kiehart and Kerry Bloom

To elucidate the dynamic and functional role of a cell within the tissue it belongs to, it is essential to understand its material properties. The cell is a viscoelastic material with highly unusual properties. Measurements of the mechanical behavior of cells are beginning to probe the contribution of constituent components to cell mechanics. Reconstituted cytoskeletal protein networks have been shown to mimic many aspects of the mechanical properties of cells, providing new insight into the origin of cellular behavior. These networks are highly nonlinear, with an elastic modulus that depends sensitively on applied stress. Theories can account for some of the measured properties, but a complete model remains elusive. DOI 10.1016DOI 10. /j.ceb.2006 Introduction Cells are highly dynamic: they crawl, change shape and divide. In many critical biological processes, cells both exert and respond to forces in their surroundings; the mechanical properties of the cell are intimately related to this behavior. Cells also continually remodel their internal structure and thereby change their mechanical properties. An integrated understanding of cell structure and mechanics is thus essential for elucidating many fundamental aspects of cell behavior, from motility to differentiation and development. Here we focus on the mechanical properties of cells and review recent developments in our understanding of the cell as a material. A variety of experimental techniques show that cells have both elastic and viscous characteristics, and thus are viscoelastic materials: their stiffness is similar to Jello, but they continue to slowly deform under a steady stress The mechanical properties of the cell are largely determined by the cytoskeleton, a biopolymer network consisting of three major components: filamentous actin (F-actin), intermediate filaments and microtubules Reconstituted cytoskeletal networks A major advantage of reconstituted networks is that their viscoelastic properties can be probed by traditional engineering approaches [3 ], as well as by more sophisticated optical methods; by measuring the time-dependent response to an imposed stress or strain, both the elastic and viscous properties can be determined. Networks of Factin are among the most widely studied reconstituted systems. As with the other cytoskeletal filaments, F-actin is a semi-flexible polymer, neither completely flexible, like more traditional synthetic polymers, nor perfectly rigid. Instead, the filaments are soft enough to have some thermally induced shape fluctuations that play an important role in their elasticity. The effects of thermal fluctuations are particularly apparent in the network elasticity at the shortest timescales, leading to a characteristic time dependence [4]; the same behavior was also recently observed in cells [5 ,6 ]. Other recent measurements of F-actin networks demonstrate the important role of filament length [7] and additional relaxation mechanisms specific to semi-flexible filaments [8]. While earlier studies elucidate the behavior of solutions of entangled Factin alone, current efforts focus primarily on the effects of crosslinking proteins and other actin-binding proteins The stress-stiffening of biopolymer networks has important implications: the magnitude of their linear elasticity is typically orders of magnitude less than that of cells; however, when prestressed into the nonlinear regime, the elasticity of these networks dramatically increases, approaching that of cells [10,12 ]. This suggests that cells themselves are prestressed into a nonlinear regime, presumably by molecular motors such as myosin. It would be particularly interesting to test the role of myosin in in vitro networks [15]. Much less is known about the mechanics of networks reconstituted from other cytoskeletal proteins. The behavior of single intermediate filaments under applied stress Measurements of cell mechanics The mechanical properties of cells are incredibly rich; understanding them is challenging as there is a diversity of experimental techniques that probe different parts of the cell and report varying responses ( The structural heterogeneity and region-to-region variation of cell properties make methods to probe local mechanical response essential. The local viscoelastic properties of a single cell can be probed through microindentation by atomic force microscopy (AFM) The cell as a material Kasza et al. 103 www.sciencedirect.com Current Opinion in Cell Biology 2007, 19: [101][102][103][104][105][106][107] or, to even higher precision, with laser particle tracking [5 ]. While this technique probes local mechanics, it suffers from uncertainties in the nature of the bead attachment to the cell, which makes determining a true magnitude for the elastic and viscous moduli difficult. Other techniques rely on endogenous structures; for example, local response is probed by the motion or deformation of microtubules Local material properties of cells are also investigated using measurements of the motion of probe particles within a cell. However, recent work [5 ] clearly shows the potential pitfalls in the interpretation of these results. To determine the elastic constant, the particle motion is assumed to be driven exclusively by thermal fluctuations; however, the activity of motor proteins and other nonequilibrium processes in cells also contribute to motion. Not considering these effects can produce erroneous results Recent experiments have highlighted the importance of the fluid properties of the cell. Any motion of the networks also entails motion of the water in which they are embedded, and this will contribute to the overall response The results from all of these techniques are beginning to provide a consistent picture: at timescales varying between a fraction of a second and several tens of seconds, the cell is a predominantly elastic material. At timescales shorter than a fraction of a second, the response reflects the effects of individual filaments and the elasticity increases [5 ,6 ]. At timescales of >30 seconds, the effects of cell remodeling Viscoelastic response can also be directly determined by deforming the whole cell [1 ,44,45]. Recent experiments demonstrate that the elasticity of a whole cell increases 104 Cell structure and dynamics , consistent with earlier experiments relating cell elasticity to internally generated prestress The prestress and elasticity of the cell, as well as its internal structure, are responsive to external cues. Recent work shows that in response to external forces applied through magnetic beads, cells stiffen in some cases Modeling cell mechanics The highly complex and heterogeneous structure of the cell makes modeling its mechanical properties very difficult. A complete model should account for all components that contribute to the mechanics of the cell, as well as the interactions between these components that result in the full 'system' behavior. There are many models that describe at least some properties, and there has been extensive work on several of these models during the past two years. One widely debated model is the 'tensegrity' model A second model to describe cell elasticity that has gained considerable traction is the 'soft glassy rheology' (SGR) model [6, The cell as a material Kasza et al. 105 Figure 4 Cells are complex materials with components under tension and compression. (a) Stress fibers in cells stained with EYFP-actin are severed by laser nanoscissors. After abscission, single stress fiber bundles snap back, exhibiting tension. Scale bar = 10 mm. Reprinted with permission fro

Germ fate determinants protect germ precursor cell division by reducing septin and anillin levels at the cell division plane.

Animal cell cytokinesis, or the physical division of one cell into two, is thought to be driven by constriction of an actomyosin contractile ring at the division plane. The mechanisms underlying cell type-specific differences in cytokinesis remain unknown. Germ cells are totipotent cells that pass genetic information to the next generation. Previously, using mutant embryos, we found that the P2 germ precursor cell is protected from cytokinesis failure and can divide with greatly reduced F-actin levels at the cell division plane. Here, we identified two canonical germ fate determinants required for P2-specific cytokinetic protection: PIE-1 and POS-1. Neither has been implicated previously in cytokinesis. These germ fate determinants protect P2 cytokinesis by reducing the accumulation of septin and anillin at the division plane, which here act as negative regulators of cytokinesis. These findings may provide insight into the regulation of cytokinesis in other cell types, especially in stem cells with high potency

Cell volume change through water efflux impacts cell stiffness and stem cell fate

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology