Microenvironmental entropy dynamics analysis reveals novel insights into Notch-Delta-Jagged decision-making mechanism.

Notch-Delta-Jagged (NDJ) signaling among neighboring cells contributes crucially to spatiotemporal pattern formation and developmental decision-making. Despite numerous detailed mathematical models, their high-dimensionality parametric space limits analytical treatment, especially regarding local microenvironmental fluctuations. Using the low-dimensional dynamics of the recently postulated least microenvironmental uncertainty principle (LEUP) framework, we showcase how the LEUP formalism recapitulates a noisy NDJ spatial patterning.

Spatiotemporal Patterning Enabled by Gene Regulatory Networks.

Spatiotemporal pattern formation plays a key role in various biological phenomena including embryogenesis and neural network formation. Though the reaction-diffusion systems enabling pattern formation have been studied phenomenologically, the biomolecular mechanisms behind these processes have not been modeled in detail. Here, we study the emergence of spatiotemporal patterns due to simple, synthetic and commonly observed two- and three-node gene regulatory network motifs coupled with their molecular diffusion in one- and two-dimensional space.

Precision of Protein Thermometry.

Temperature sensing is a ubiquitous cell behavior, but the fundamental limits to the precision of temperature sensing are poorly understood. Unlike in chemical concentration sensing, the precision of temperature sensing is not limited by extrinsic fluctuations in the temperature field itself. Instead, we find that precision is limited by the intrinsic copy number, turnover, and binding kinetics of temperature-sensitive proteins.

Intermediate adhesion maximizes migration velocity of multicellular clusters.

Collections of cells exhibit coherent migration during morphogenesis, cancer metastasis, and wound healing. In many cases, bigger clusters split, smaller subclusters collide and reassemble, and gaps continually emerge. The connections between cell-level adhesion and cluster-level dynamics, as well as the resulting consequences for cluster properties such as migration velocity, remain poorly understood.

Statistics of correlated percolation in a bacterial community.

Signal propagation over long distances is a ubiquitous feature of multicellular communities, but cell-to-cell variability can cause propagation to be highly heterogeneous. Simple models of signal propagation in heterogenous media, such as percolation theory, can potentially provide a quantitative understanding of these processes, but it is unclear whether these simple models properly capture the complexities of multicellular systems. We recently discovered that in biofilms of the bacterium Bacillus subtilis, the propagation of an electrical signal is statistically consistent with percolation theory, and yet it is reasonable to suspect that key features of this system go beyond the simple assumptions of basic percolation theory.

Ultrasensitivity and fluctuations in the Barkai-Leibler model of chemotaxis receptors in Escherichia coli.

A stochastic version of the Barkai-Leibler model of chemotaxis receptors in Escherichia coli is studied here with the goal of elucidating the effects of intrinsic network noise in their conformational dynamics. The model was originally proposed to explain the robust and near-perfect adaptation of E. coli observed across a wide range of spatially uniform attractant/repellent (ligand) concentrations.

Zero-order ultrasensitivity: a study of criticality and fluctuations under the total quasi-steady state approximation in the linear noise regime.

Zero-order ultrasensitivity (ZOU) is a long known and interesting phenomenon in enzyme networks. Here, a substrate is reversibly modified by two antagonistic enzymes (a 'push-pull' system) and the fraction in modified state undergoes a sharp switching from near-zero to near-unity at a critical value of the ratio of the enzyme concentrations, under saturation conditions. ZOU and its extensions have been studied for several decades now, ever since the seminal paper of Goldbeter and Koshland (1981); however, a complete probabilistic treatment, important for the study of fluctuations in finite populations, is still lacking.