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Othmer, H.

Publications and source records attributed to Othmer, H..

3 recordsLinked to original sources

The Role of Cytonemes and Diffusive Transport in the Establishment of Morphogen Gradients

Spatial distributions of morphogens provide positional information in developing systems, but how the distributions are established and maintained remains an open problem. Transport by diffusion has been the traditional mechanism, but recent experimental work has shown that cells can also communicate by filopodia-like structures called cytonemes that make direct cell-to-cell contacts. Here we investigate the roles each may play individually in a complex tissue and how they can jointly establish a reliable spatial distribution of a morphogen. To this end, we formulate models that capture fundamental aspects of various cytoneme-based transport mechanisms. In simple cases, exact solutions are attainable, and in more complex cases, we discuss results of numerical simulations.

biophysics↗

A Stochastic Model for Actin Waves in Eukaryotic Cells

A stochastic model of spontaneous actin wave formation in eukaryotic cells that includes positive feedback between the actin network and filament nucleating factors on the membrane is developed and analyzed. Simulation results show that the model can produce a variety of actin network behavior depending on the conditions. Actin spots of diameter about 0.5 {micro}m can be formed and persist for tens of seconds at low actin concentrations, and these spots may either shrink and die or grow and develop into fully-developed propagating waves. The model correctly captures the vertical profile of actin waves along line scans through wave fronts, as well as the separation between the region enclosed by circular actin waves and the external area. Our results show how the complicated actin behavior depends on the amounts and state of various membrane molecules. Author SummaryLocomotion of eukaryotic cells is a complex process that involves the spatio-temporal control and integration of a number of sub-processes, including the transduction of chemical or mechanical signals from the environment, local and global modification of the cytoskeleton, and translation of the intra- and extracellular signals into a mechanical response. In view of the complexity of the processes, understanding how force generation and mechanical interactions with the surroundings are controlled in space and time to produce cell-level movement is a major challenge. Recent experimental work has shown that a variety of actin waves propagate within cells, both under normal conditions and during re-building of the cytoskeleton following its disruption. Controlled disruption and re-building of the actin network has led to new insights into the key components involved in actin waves, and here we develop a stochastic model that can qualitatively and quantitatively describe the dynamical behavior of such waves.

systems biology↗

Getting in shape and swimming: the role of cortical forces and membrane heterogeneity in eukaryotic cells

Recent research has shown that motile cells can adapt their mode of propulsion to the mechanical properties of the environment in which they find themselves - crawling in some environments while swimming in others. The latter can involve movement by blebbing or other cyclic shape changes, and both highly-simplified and more realistic models of these modes have been studied previously. Herein we study swimming that is driven by membrane tension gradients that arise from flows in the actin cortex underlying the membrane, and does not involve imposed cyclic shape changes. Such gradients can lead to a number of different characteristic cell shapes, and our first objective is to understand how different distributions of membrane tension influence the shape of cells in a quiescent fluid. We then analyze the effects of spatial variation in other membrane properties, and how they interact with tension gradients to determine the shape. We also study the effect of fluid-cell interactions and show how tension leads to cell movement, how the balance between tension gradients and a variable bending modulus determine the shape and direction of movement, and how the efficiency of movement depends on the properties of the fluid and the distribution of tension and bending modulus in the membrane.\n\nDedicated to the memory of Karl P. Hadeler, a pioneer in the field of Mathematical Biology and a friend and mentor to many.

biophysics↗