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Biomedical subjects

G F Oster

Publications and source records attributed to G F Oster.

28 records · Page 2Linked to original sources

Generation of biological pattern and form.

We propose two models for pattern formation in early embryogenesis. The first deals with patterns in motile mesenchymal cells; the second treats patterns in epithelial sheets. In the mesenchymal model, cells exert tractions which deform the extracellular matrix within which they move. This in turn affects their motion. The model field equations are formulated and analysed, and applied to two widely studied phenomena: skin-organ primordia for feather and scale patterns, and the development of cartilage patterns in limb bone formation. The model for epithelial pattern formation consists of viscoelastic field equations with a calcium-controlled contraction trigger. Preliminary analysis is presented which demonstrates the existence of travelling wave solutions.

Animals↗

On the crawling of cells.

Motile cells moving in vitro do so via a characteristic motile appendage, the lamellipod, a broad, flat region of the cell cytoplasm which extends ahead of the moving cell, and which is devoid of organelles. I describe here a mechanochemical model for how the lamellipod propels the cell forward. The propulsive force for the spreading of the lamella derives from the swelling pressure of the cytogel within the lamellipod. A local change in ionic conditions - caused by a leak through the leading membrane - activates solating factors, which upsets the equilibrium between the gel osmotic pressure and its elasticity. Subsequently, regelling and contraction pull the cell forward. The model is in accordance with a diverse array of experimental observations on cell motility, and suggests a common physical mechanism underlying a variety of cell motility phenomena.

Actomyosin↗

Mechanical aspects of mesenchymal morphogenesis.

Many embryonic cells generate substantial contractile forces as they spread and crawl. These forces mechanically deform each cell's local environment, and the resulting distortions can alter subsequent cell movements by convection and the mechanisms of contact guidance and haptotaxis. Here we develop a model for the cumulative effects of these cell-generated forces and show how they can lead to the formation of regular large-scale patterns in cell populations. This model leads to several predictions concerning the effects of cellular and matrix properties on the resulting patterns. We apply the model to two widely studied morphogenetic processes: (a) patterns of skin-organ primordia, especially feather germ formation, and (b) the condensation of cartilagenous skeletal rudiments in the developing vertebrate limb.

Animals↗

Optimal strategies in immunology. II. B memory cell production.

After a first encounter with most antigens, the immune system responds to susequent encounters with a faster, more efficient and more strenuous antibody response. The memory of previous antigen contacts is carried by lymphocytes. Expanding on the model developed in Part 1 of this paper, we examine the optimal strategy available to the immune system for B memory cell production. We again find that the strategy should be of the bang-bang variety. The model we consider assumes that antigen triggers a subpopulation of B-lymphocytes. These triggered lymphocytes can proliferate and secrete modest amounts of antibody, or differentiate into non-dividing plasma cells which secrete large amounts of antibody, or differentiate into non-antibody secreting memory cells. Given injections of antigen at two widely spaced times we compute the strategy which minimizes a linear combination of the primary and secondary response times. We find that for all biologically reasonable parameter values the best strategies are ones in which memory cells are produced at the end of the primary response. Exerimental results which bear on the actual strategies employed are discussed.

Antibody Formation↗

Optimal strategies in immunology. I. B-cell differentiation and proliferation.

The optimal strategy available to the immune system for responding to a non-replicating thymus-independent antigen is examined. By applying Pontryagin's maximum principle to a set of mathematical models of lymphocyte populations and their antibody production, it is found that the optimal strategy of bang-bang control appears robust. In a variety of structurely related biological models, similar behaviour is observed. The models that we consider assume that antigen triggers a population of B-lymphocytes. These triggered lymphocytes can either proliferate and secrete modest amounts of antibody or differentiate into nondividing plasma cells which secrete large amounts of antibody. For biologically reasonable parameter values it is found that for low doses of antigen, immediate differentiation into plasma cells is optimal, while for high antigen doses a proliferative state followed by differentiation is the best strategy.

Antibody Formation↗