Collaborative Project: Physical Mechanisms of Morphogeneis

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Newman 96-03838 The behavior of tissues during development, wound healing, tumor invasion and other morphogenetic events depends, in part, on quantitative relationships among physical properties such as surface tension, viscosity and elasticity that such tissues share with all semi-solid materials. Drs. Newman and Forgacs propose to extend their characterization of the viscoelastic properties of model tissue systems based on assembling collagen matrices, using the oscillating disk and magnetic tweezers microrheometers. These techniques will permit the simultaneous analysis of viscosity and elastic modulus of assembling matrices. They will also permit them to analyze the dependence of these properties on the presence of cell-sized particles with defined surface characteristics, on living cells that interact with collagen, and on cells whose interaction with the collagen matrix is abrogated by the presence of anti-integrin antibodies. They also plan to establish conditions under which a parallel plate tissue compression apparatus, previously used to measure effective surface tensions of embryonic tissues, can be used to measure viscosities of these tissues. This apparatus will then be used to measure the surface tensions and viscosities of fore and hind limb bud tissues, which they have previously shown to exhibit distinctive physical behaviors and extracellular matrix organization, and of such tissues which have been genetically modified to have altered extracellular matrix organization. Viscoelastic characteristics of embryonic flank tissue will be compared with those of limb tissues to test the hypothesis that the emergence of the limb bud from the embryonic flank is due to development of tissue immiscibility. Viscosity of normal and retinoic acid-treated limb tissues will be analyzed to test the hypothesis that the effect of this substance on limb development is mediated, in part, by changes in viscosity. This work will provide new knowledge concerning physical mechanisms of morphogenes is and their relationship to the expression and organization of specific gene products.