Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity.

A variety of cytomorphological features, architectural patterns and stromal changes may be observed in malignant melanomas. Hence, melanomas may mimic carcinomas, sarcomas, benign stromal tumours, lymphomas, plasmacytomas and germ cell tumours. Melanomas may be composed of large pleomorphic cells, small cells, spindle cells and may contain clear, signet-ring, pseudolipoblastic, rhabdoid, plasmacytoid or balloon cells. Various inclusions and phagocytosed material may be present in their cytoplasm. Nuclei may show bi- or multi-nucleation, lobation, inclusions, grooving and angulation. Architectural variations include fasciculation, whorling, nesting, trabeculation, pseudoglandular/pseudopapillary/pseudofollicular, pseudorosetting and angiocentric patterns. Myxoid or desmoplastic changes and very rarely pseudoangiosarcomatous change, granulomatous inflammation or osteoclastic giant cell response may be seen in the stroma. The stromal blood vessels may exhibit a haemangiopericytomatous pattern, proliferation of glomeruloid blood vessels and perivascular hyalinization. Occasionally, differentiation to nonmelanocytic structures (Schwannian, fibro-/myofibroblastic, osteocartilaginous, smooth muscle, rhabdomyoblastic, ganglionic and ganglioneuroblastic) may be observed. Typically melanomas are S100 protein, NKIC3, HMB-45, Melan-A and tyrosinase positive but some melanomas may exhibit an aberrant immunophenotype and may express cytokeratins, desmin, smooth muscle actin, KP1 (CD68), CEA, EMA and VS38. Very rarely, neurofilament protein and GFAP positivity may be seen.

To understand how the mechanical properties of tissues emerge from interactions of multiple cells, we measure traction stresses of cohesive colonies of 1–27 cells adherent to soft substrates. We find that traction stresses are generally localized at the periphery of the colony and the total traction force scales with the colony radius. For large colony sizes, the scaling appears to approach linear, suggesting the emergence of an apparent surface tension of the order of 10−3 N/m. A simple model of the cell colony as a contractile elastic medium coupled to the substrate captures the spatial distribution of traction forces and the scaling of traction forces with the colony size.

This series documents continuing difficulties in the diagnosis of EMMT. Even well differentiated tumours are frequently mistakenly diagnosed as malignant lymphomas when they present without any history of antecedent myeloproliferative disorder. Careful evaluation of morphology for evidence of myeloid differentiation and a high index of suspicion when confronted with a less differentiated neoplasm are required to avoid this important diagnostic error. We suggest that a panel which includes chloroacetate-esterase, myeloperoxidase, lysozyme and CD43, together with other B- and T-lineage markers, in particular CD79a and CD3 should be used to confirm the diagnosis.

22The collective behaviour of cells in epithelial tissues is dependent on their 23 mechanical properties. However, the contribution of tissue mechanics to wound 24 90 cell-based models, such as vertex models 26,27 , have rarely been applied to replicate 91 in vivo wound healing dynamics. We model each cell in the tissue as a two-92 dimensional polygon carrying variable tension on their edges, with bulk elasticity and 93 peripheral contractility ( Supplementary Fig. 2a-b, methods). We parameterised the 94 model so that edges contacting the wound gradually increase in tension compared to 95 5 the surrounding tissue, to mimic the assembly of the contractile actomyosin purse 96 string, causing wound edge junctions to reduce in length. To capture experimentally 97 observed fluctuations in junctional and purse-string MyoII 28 , we introduced 98 fluctuations in line tension at cell-cell interfaces and in the purse-string 99 ( Supplementary Fig. 2d). Without introducing intercalation events into the model, 100 simulated wounds are unable to close (Figs. 2a, c, Supplementary Video 3). By 101 contrast, when intercalations are enabled in the model ( Supplementary Fig. 2c, see 102 methods), wounds are able to close (Figs. 2b, d, Supplementary Video 4), supporting 103 our hypothesis that intercalations at the wound edge are necessary to drive wound 104 closure. 105The vertex model predicts that in the absence of intercalation, cells around 106 the wound become more elongated towards the centre of the wound (Fig. 2e) than in 107 simulations with intercalations enabled (Fig. 2f). In both cases, the cells initially 108 elongate as the purse-string contracts the wound. As cells begin to intercalate away 109 from the wound edge their shapes relax, reducing the elongation over time. Towards 110 the end of wound closure, many intercalations occur (Fig. 2b), at which point the 111 elongation rapidly decreases, and the cells return to a fully relaxed state after healing 112 (Fig. 2f). With intercalations disabled, the cells remain highly elongated ( Fig. 2e). 113This led us to hypothesise that wound edge intercalations play a crucial role in 114 maintaining cell shape and tissue patterning. Indeed, wing disc cells appear regularly 115 packed immediately after wound closure (Fig. 3a) and the polygon distribution of 116 wound edge cells is restored upon healing (Fig. 3b). The seamless closure we 117 observe is distinct from a number of in vivo 22,29 and in vitro 5,30 systems that can form 118 visible scar-like rosette structures upon closure. To test our vertex model's prediction 119 that intercalation preserves cell shape, we quantified cell elongation in the first three 120 6 rows of cells away from the wound in wing discs ( Fig. 3c, Supplementary Video 5).

No abstract

Rod-shaped bacterial cells can readily adapt their lengths and widths in response to environmental changes. While many recent studies have focused on the mechanisms underlying bacterial cell size control, it remains largely unknown how the coupling between cell length and width results in robust control of rod-like bacterial shapes. In this study we uncover a conserved surface-to-volume scaling relation in Escherichia coli and other rod-shaped bacteria, resulting from the preservation of cell aspect ratio. To explain the mechanistic origin of aspect-ratio control, we propose a quantitative model for the coupling between bacterial cell elongation and the accumulation of an essential division protein, FtsZ. This model reveals a mechanism for why bacterial aspect ratio is independent of cell size and growth conditions, and predicts cell morphological changes in response to nutrient perturbations, antibiotics, MreB or FtsZ depletion, in quantitative agreement with experimental data.

The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid phase of actin filaments in the presence of the physiological cross-linker, filamin. Filamin condenses short actin filaments into spindle-shaped droplets, or tactoids, with shape dynamics consistent with a continuum model of anisotropic liquids. We find that cross-linker density controls the droplet shape and deformation timescales, consistent with a variable interfacial tension and viscosity. Near the liquid-solid transition, cross-linked actin bundles show behaviors reminiscent of fluid threads, including capillary instabilities and contraction. These data reveal a liquid droplet phase of actin, demixed from the surrounding solution and dominated by interfacial tension. These results suggest a mechanism to control organization, morphology, and dynamics of the actin cytoskeleton.actin | phase separation | liquid crystal | cytoskeleton T he cellular cytoplasm is a hierarchical array of diverse, soft materials assembled from biological molecules that work in concert to support cell physiology (1). The actin cytoskeleton constitutes a spectrum of materials constructed from the semiflexible polymer actin (F-actin) that are crucial in diverse physical processes ranging from cell division and migration to tissue morphogenesis (2, 3). Cross-linking and regulatory proteins assemble actin filaments into bundles and networks with varied composition, mechanics, and physiological function (4). The mechanical properties of actin assemblies regulate force generation and transmission to dynamically control morphogenic processes from the subcellular to tissue length scales (5, 6).A mechanistic understanding of cytoplasmic mechanics is obscured by the rich complexity of in vivo cytoskeletal assemblies (7) and has been investigated via in vitro model systems (8, 9). Vastly different material properties have been accessed through varying filament length, concentration, and cross-linking. For semidilute concentrations of long actin filaments (>1 μm), the mean spacing between actin filaments, or mesh size, is much smaller than the filament length. In this case, cross-linking proteins mechanically constrain actin filaments to result in space-spanning networks that are viscoelastic gels (10). The structure of cross-linked actin networks is kinetically determined, reflecting a metastable state (11, 12) that requires motor-driven stresses for significant shape changes (13). In contrast, highly concentrated solutions of short actin filaments (<1 μm) align due to entropic effects and form equilibrium liquid crystal phases (14). Liquid crystal theory has been introduced as a framework to understand actin cortex mechanics and mitotic spindle shape (5, 15), but the existence of liquid crystal-like phases at physiological conditions is uncertain.Liquid-like phases of proteins and nucleic acids have been found within the cytoplasm and are thought to be important in subcellular...