Browsing by Author "Bozorgui, Behnaz"

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    Development of Morphogen Gradients with Spatially Varying Degradation Rates
    (American Chemical Society, 2016) Teimouri, Hamid; Bozorgui, Behnaz; Kolomeisky, Anatoly B.; Center for Theoretical Biological Physics
    Successful biological development via spatial and temporal regulations of cell differentiation relies on the action of multiple signaling molecules that are known as morphogens. It is now well established that biological signaling molecules create nonuniform concentration profiles, called morphogen gradients, that activate different genes, leading to patterning in the developing organisms. The current view of the formation of morphogen gradients is that it is a result of complex reaction–diffusion processes that include production, diffusion, and degradation of signaling molecules. Recent studies also suggest that the degradation of morphogens is a critically important step in the whole process. We develop a theoretical model that allows us to investigate the role of a spatially varying degradation in the formation of morphogen gradients. Our analysis shows that the spatial inhomogeneities in degradation might strongly influence the dynamics of formation of signaling profiles. Physical–chemical mechanisms of the underlying processes are discussed.
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    Physical-chemical mechanisms of pattern formation during gastrulation
    (AIP Publishing, 2018) Bozorgui, Behnaz; Kolomeisky, Anatoly B.; Teimouri, Hamid; Center for Theoretical Biological Physics
    Gastrulation is a fundamental phase during the biological development of most animals when a single layer of identical embryo cells is transformed into a three-layer structure, from which the organs start to develop. Despite a remarkable progress in quantifying the gastrulation processes, molecular mechanisms of these processes remain not well understood. Here we theoretically investigate early spatial patterning in a geometrically confined colony of embryonic stem cells. Using a reaction-diffusion model, a role of Bone-Morphogenetic Protein 4 (BMP4) signaling pathway in gastrulation is specifically analyzed. Our results show that for slow diffusion rates of BMP4 molecules, a new length scale appears, which is independent of the size of the system. This length scale separates the central region of the colony with uniform low concentrations of BMP molecules from the region near the colony edge where the concentration of signaling molecules is elevated. The roles of different components of the signaling pathway are also explained. Theoretical results are consistent with recent in vitro experiments, providing microscopic explanations for some features of early embryonic spatial patterning. Physical-chemical mechanisms of these processes are discussed.
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    Theoretical analysis of degradation mechanisms in the formation of morphogen gradients
    (AIP Publishing LLC., 2015) Bozorgui, Behnaz; Teimouri, Hamid; Kolomeisky, Anatoly B.; Center for Theoretical Biological Physics
    Fundamental biological processes of development of tissues and organs in multicellular organisms are governed by various signaling molecules, which are called morphogens. It is known that spatial and temporal variations in the concentration profiles of signaling molecules, which are frequently referred as morphogen gradients, lead to a cell differentiation via activating specific genes in a concentration-dependent manner. It is widely accepted that the establishment of the morphogen gradients involves multiple biochemical reactions and diffusion processes. One of the critical elements in the formation of morphogen gradients is a degradation of signaling molecules. We develop a new theoretical approach that provides a comprehensive description of the degradation mechanisms. It is based on the idea that the degradation works as an effective potential that drives the signaling molecules away from the source region. Utilizing the method of first-passage processes, the dynamics of the formation of morphogen gradients for various degradation mechanisms is explicitly evaluated. It is found that linear degradation processes lead to a dynamic behavior specified by times to form the morphogen gradients that depend linearly on the distance from the source. This is because the effective potential due to the degradation is quite strong. At the same time, nonlinear degradation mechanisms yield a quadratic scaling in the morphogen gradients formation times since the effective potentials are much weaker. Physical-chemical explanations of these phenomena are presented.