Collaborative Project: Physical Mechanisms of Morphogeneis

Newman 96-03838组织在发育、伤口愈合、肿瘤侵袭和其他形态发生事件中的行为部分取决于这些组织与所有半固体材料共享的表面张力、粘度和弹性等物理性质之间的定量关系。Newman博士和Forgacs博士建议扩展他们对基于组装胶原基质的模型组织系统的粘弹性特性的表征，使用摆动圆盘和磁性镊子微观流变仪。这些技术将允许同时分析组装矩阵的粘性和弹性模数。他们还将允许他们分析这些特性对具有明确表面特征的细胞大小颗粒的存在、与胶原相互作用的活细胞以及与胶原基质相互作用被抗整合素抗体存在的细胞的依赖性。他们还计划建立一种条件，在这种条件下，以前用于测量胚胎组织有效表面张力的平行板组织压力仪可以用来测量这些组织的粘度。然后，该仪器将被用来测量前肢和后肢芽组织的表面张力和粘度，这些组织以前已经被证明具有独特的物理行为和细胞外基质组织，以及这些组织已经被转基因改变了细胞外基质组织。将胚胎侧翼组织的粘弹性特性与四肢组织的粘弹性特性进行比较，以验证肢体芽从胚胎侧翼出现是由于组织不混溶的发展的假设。将分析正常和维甲酸处理的肢体组织的粘度，以检验这种物质对肢体发育的影响部分是通过粘度变化来调节的假设。这项工作将提供有关形态发生的物理机制以及它们与特定基因产物的表达和组织的关系的新知识。

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.