Morphogen-regulated contact-mediated signaling between cells can drive the transitions underlying body segmentation in vertebrates.

We propose a unified mechanism that reproduces the sequence of dynamical transitions observed during somitogenesis, the process of body segmentation during embryonic development, that is invariant across all vertebrate species. This is achieved by combining inter-cellular interactions mediated via receptor-ligand coupling with global spatial heterogeneity introduced through a morphogen gradient known to occur along the anteroposterior axis. Our model reproduces synchronized oscillations in the gene expression in cells at the anterior of the presomitic mesoderm as it grows by adding new cells at its posterior, followed by travelling waves and subsequent arrest of activity, with the eventual appearance of somite-like patterns. This framework integrates a boundary-organized pattern formation mechanism, which uses positional information provided by a morphogen gradient, with the coupling-mediated self-organized emergence of collective dynamics, to explain the processes that lead to segmentation.

Precision of morphogen-driven tissue patterning during development is enhanced through contact-mediated cellular interactions.

Cells in developing embryos reliably differentiate to attain location-specific fates, despite fluctuations in morphogen concentrations that provide positional information and in molecular processes that interpret it. We show that local contact-mediated cell-cell interactions utilize inherent asymmetry in the response of patterning genes to the global morphogen signal yielding a bimodal response. This results in robust developmental outcomes with a consistent identity for the dominant gene at each cell, substantially reducing the uncertainty in the location of boundaries between distinct fates.

Contact-mediated signaling enables disorder-driven transitions in cellular assemblies.

We show that, when cells communicate by contact-mediated interactions, heterogeneity in cell shapes and sizes leads to qualitatively distinct collective behavior in the tissue. For intercellular coupling that implements lateral inhibition, such disorder-driven transitions can substantially alter the asymptotic pattern of differentiated cells by modulating their fate choice through changes in the neighborhood geometry. In addition, when contact-induced signals influence inherent cellular oscillations, disorder leads to the emergence of functionally relevant partially-ordered dynamical states.

Contact-mediated cellular communication supplements positional information to regulate spatial patterning during development.

Development in multicellular organisms is marked by a high degree of spatial organization of the cells attaining distinct fates in the embryo. Recent experiments showing that suppression of intercellular interactions can alter the spatial patterns arising during development suggest that cell fates cannot be determined by the exclusive regulation of differential gene expression by morphogen gradients (the conventional view encapsulated in the French flag model). Using a mathematical model that describes the receptor-ligand interaction between cells in close physical proximity, we show that such intercellular signaling can regulate the process of selective gene expression within each cell, allowing information from the cellular neighborhood to influence the process by which the thresholds of morphogen concentration that dictate cell fates adaptively emerge. This results in local modulations of the positional cues provided by the global field set up by the morphogen, allowing interaction-mediated self-organized pattern formation to complement boundary-organized mechanisms in the context of development.

Disorder in cellular packing can alter proliferation dynamics to regulate growth.

The mechanisms by which an organ regulates its growth are not yet fully understood, especially when the cells are closely packed as in epithelial tissues. We explain growth arrest as a collective dynamical transition in coupled oscillators on disordered lattices. As the cellular morphologies become homogeneous over the course of development, the signals induced by cell-cell contact increase beyond a critical value that triggers coordinated cessation of the cell-cycle oscillators driving cell division. Thus, control of cell proliferation is causally related to the geometry of cellular packing.

Emergence of frustration signals systemic risk.

We show that the emergence of systemic risk in complex systems can be understood from the evolution of functional networks representing interactions inferred from fluctuation correlations between macroscopic observables. Specifically, we analyze the long-term collective dynamics in the New York Stock Exchange, the largest financial market in the world, for almost a century and show that periods marked by systemic crisis are associated with emergence of frustration. This is indicated by the loss of structural balance in the networks of interaction between stocks. Moreover, the mesoscopic organization of the networks during these periods exhibits prominent core-periphery organization. This suggests an increased degree of coherence in the collective dynamics of the system, which is reinforced by our observation of the transition to delocalization in the dominant eigenmodes when the systemic risk builds up. While frustration has been associated with phase transitions in physical systems such as spin glasses, its role as a signal for systemic risk buildup leading to severe crisis as shown here provides a novel perspective into the dynamical processes leading to catastrophic failures in complex systems.

Role of actin filaments in correlating nuclear shape and cell spreading.

It is well known that substrate properties like stiffness and adhesivity influence stem cell morphology and differentiation. Recent experiments show that cell morphology influences nuclear geometry and hence gene expression profile. The mechanism by which surface properties regulate cell and nuclear properties is only beginning to be understood. Direct transmission of forces as well as chemical signalling are involved in this process. Here, we investigate the formal aspect by studying the correlation between cell spreading and nuclear deformation using Mesenchymal stem cells under a wide variety of conditions. It is observed that a robust quantitative relation holds between the cell and nuclear projected areas, irrespective of how the cell area is modified or when various cytoskeletal or nuclear components are perturbed. By studying the role of actin stress fibers in compressing the nucleus we propose that nuclear compression by stress fibers can lead to enhanced cell spreading due to an interplay between elastic and adhesion factors. The significance of myosin-II in regulating this process is also explored. We demonstrate this effect using a simple technique to apply external compressive loads on the nucleus.