Biological Fluid Dynamics in Morphogenesis

形态发生中的生物流体动力学

• 批准号: 0201094
• 负责人: Sharon Lubkin
• 金额: --
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0201094&HistoricalAwards=false
• 关键词: Biological; Fluid; Dynamics; Morphogenesis

This research will develop models of the mechanical aspects of shape change in (1) cylindrical fiber-reinforced hydrostats, (2) pattern formation by traction forces in mesenchymal tissues during development and remodeling, and (3) glandular branching morphogenesis. In this Stokesian multiphase area of biological fluid dynamics, there is no inertia, but there are forces across interfaces and transfers of forces between the fluids and fibers embedded in the fluids. In some applications, the models have multiple viscous fluids separated by active interfaces, and in others, the models have a single fluid whose motion and material properties are coupled with the motion of contractile fibers. The models will be used to gain a better understanding of the anisotropic behavior of cylindrical hydrostats (trunks, tentacles, and tongues). They will be used to increase understanding of the mechanical instabilities and pattern formation which can emerge when cells modify their extracellular matrix by moving through it or pulling on it. They will also be used to help define the developmental implications of mechanical hypotheses about how branched tubular structures (like lungs) form in the body. Some results will generate interpretations of theories, some will suggest experiments to test the implications of theories, and some will suggest industrial applications of biomechanical principles. The project will also develop the finite difference numerical methods necessary to solve the partial differential equations arising from modeling the physical forces in these tissues. The development of robust three-dimensional algorithms for the solution of biological fluid dynamics problems will be key to the effective modeling of dozens of problems in the mechanics of cell motion and tissue remodeling.This project involves several biomedical problems in the dynamics of tissues. At all stages of an organism's existence there are mechanical forces at work. How does a completely round egg get to be a very complicated-looking human being, with limbs and eyes and ducts and glands and a wrinkled brain? There are genes that switch on and off, but that is not the whole story. An airplane has switches too, but to understand how it really works, we need to study fluid mechanics - the physical forces that lift, stabilize, and occasionally disturb the craft. Fluid dynamics is equally relevant to biology. As an organism - or part of it - is growing, it creates physical forces, and is shaped by physical forces. The science of Tissue Dynamics is relatively new, and requires expertise in many areas. A biological modeler, a numerical analyst, a developmental biologist, and an industrial researcher have teamed up to study the biomechanics of tissues which are changing their shape, size, strength, orientation, and function. Results of the work should increase our understanding of processes in developmental biology, wound healing, cancer, vascular health and disease, and many other areas of biomedicine involving tissues. This grant is made under the Joint DMS/NIGMS Initiative to Support Research Grants in the Area of Mathematical Biology. This is a joint competition sponsored by the Division of Mathematical Sciences (DMS) at the National Science Foundation and the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health.

这项研究将建立(1)圆柱形纤维增强水晶器的形状变化的力学方面的模型，(2)在发育和重塑过程中间充质组织中牵引力形成的图案，以及(3)腺体分支的形态发生。在生物流体动力学的斯托克斯多相区，没有惯性，但存在跨界面的力，以及流体和嵌入在流体中的纤维之间的力传递。在某些应用中，模型具有由活动界面分隔的多个粘性流体，而在另一些应用中，模型具有单个流体，其运动和材料特性与收缩纤维的运动相耦合。这些模型将被用来更好地了解圆柱形静水器(树干、触须和舌头)的各向异性行为。它们将被用来增加对细胞通过或拉动细胞外基质来修改细胞外基质时可能出现的机械不稳定性和图案形成的理解。它们还将被用来帮助定义关于人体内分支管状结构(如肺)如何形成的力学假说的发育意义。一些结果将产生对理论的解释，一些结果将建议进行实验来测试理论的含义，还有一些结果将建议生物力学原理的工业应用。该项目还将开发必要的有限差分数值方法，以求解由对这些组织中的物理力进行建模而产生的偏微分方程组。开发解决生物流体动力学问题的稳健三维算法将是有效模拟细胞运动力学和组织重建中数十个问题的关键。该项目涉及组织动力学中的几个生物医学问题。在有机体存在的所有阶段，都有机械力在起作用。一个完全圆的鸡蛋怎么会变成一个看起来非常复杂的人，有四肢、眼睛、导管、腺体和皱纹的大脑？有基因可以开启和关闭，但这并不是故事的全部。飞机也有开关，但要了解它的真正工作原理，我们需要研究流体力学--提升、稳定飞机的物理力，有时还会干扰飞机。流体动力学与生物学同样相关。当一个有机体--或它的一部分--在生长时，它会产生物理力量，并由物理力量塑造。组织动力学是一门相对较新的学科，需要很多领域的专业知识。一名生物模型师、一名数值分析员、一名发育生物学家和一名工业研究人员联合起来，研究正在改变其形状、大小、强度、方向和功能的组织的生物力学。这项工作的结果应该会增加我们对发育生物学、伤口愈合、癌症、血管健康和疾病以及涉及组织的许多其他生物医学领域的过程的理解。这笔赠款是在DMS/NIGMS联合倡议下提供的，以支持数学生物学领域的研究资助。这是一项由国家科学基金会数学科学部(DMS)和国立卫生研究院(NIGMS)国家普通医学研究所(NIGMS)主办的联合竞赛。