COLLABORATIVE PROJECT: Physical Mechanisms of Morphogenesis

Forgacs 97-10010 组织在发育、伤口愈合、肿瘤侵袭和其他形态发生事件期间的行为部分地取决于这些组织与所有半固体材料共享的物理性质（例如表面张力、粘度和弹性）之间的定量关系。Forgacs和纽曼博士建议扩展他们的表征模型组织系统的粘弹性的基础上组装胶原蛋白基质，使用振荡盘和磁镊微流变仪。这些技术将允许同时分析组装矩阵的粘度和弹性模量。他们还将允许他们分析这些特性对具有确定的表面特征的细胞大小的颗粒的存在的依赖性，对与胶原蛋白相互作用的活细胞的依赖性，以及对与胶原蛋白基质的相互作用被抗整合素抗体的存在所消除的细胞的依赖性。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缩装置可以用于测量这些组织的粘度。然后，该装置将用于测量前、后肢芽组织的表面张力和粘度，它们先前已经显示出表现出独特的物理行为和细胞外基质组织，以及已经被遗传修饰以具有改变的细胞外基质组织的这些组织。将胚胎侧腹组织的粘弹特性与肢体组织的粘弹特性进行比较，以检验肢体芽从胚胎侧腹出现是由于组织不混溶的发展而引起的假设。将分析正常和维甲酸处理的肢体组织的粘度，以检验该物质对肢体发育的影响部分由粘度变化介导的假设。这项工作将提供新的知识形态发生的物理机制及其与特定基因产物的表达和组织的关系。

Forgacs 97-10010 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. Forgacs and Newman 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.