Mathematical Sciences: Mathematical Models in Cellular & Developmental Biology

这位研究人员和他的同事通过数学建模和计算机模拟研究了几种涉及细胞和细胞器运动的机械力化学现象。特别是，他们专注于有偏见的随机运动在两个组织层面上创造秩序的作用。在细胞/组织水平上，他们研究了表面上随机的细胞运动如何通过边界抑制和细胞间通讯自组织成组织几何形状。在分子/细胞水平上，他们研究了几种细胞内的运动现象，这些现象似乎是通过使用化学键能量来棘轮分子组装和拆卸来从随机的热运动中提取功。这项研究旨在研究细胞在形态发生过程中如何移动和改变形状，以及大分子如何跨细胞膜运输的基本问题。这些问题对基本理解很重要，也对伤口愈合和组织发育等问题有影响。在核糖体合成蛋白质的过程中和之后，新生的多肽链必须通过内膜运输到细胞内的隔间，如内质网和线粒体。这是如何实现的是一个谜，因为它似乎是在缺乏新陈代谢能量来源的情况下进行的，例如核苷酸水解。研究人员提出了一种解释这一过程的机制，其基础是氨基酸链的热运动可能会被任何使链难以倒退的过程所偏向。这种过程的例子是伴侣蛋白的结合、糖基化和/或链折叠。他们认为，细胞内单核细胞增多性李斯特菌的推进机制是另一个通过棘轮布朗运动起作用的过程。这种细菌通过构建一条交叉连接的肌动蛋白细丝尾巴来驱动自己。他们建议通过模拟尾部组装和细菌的布朗运动的耦合动力学来模拟这一过程。

The investigator and his colleague study by mathematical modeling and computer simulation several phenomena dealing with the mechanochemistry of cell and organelle motions. In particular, they focus on the role of biased random motions in creating order at two levels of organization. At the cell/tissue level they investigate how apparently random cell motions can self organize into tissue geometries via boundary inhibitions and intercellular communication. At the molecular/cell level they examine several intracellular motility phenomena that appear to extract work from random thermal motions by employing chemical bond energy to ratchet molecular assembly and disassembly. This study aims at basic questions about how cells move and change shape during morphogenesis, and how macromolecules are transported across cell membranes. The issues are important for fundamental understanding, and also have implications for such problems as wound healing and the development of tissues. During and after protein synthesis on ribosomes the nascent polypeptide chains must be transported across internal membranes into intracellular compartments such as endoplasmic reticula and mitochondria. How this is accomplished is a mystery, for it appears to proceed in the absence of a metabolic energy source such as nucleotide hydrolysis. The investigators propose a mechanism to explain this process based on the idea that the thermal motions of the amino acid chain can be biased by any process that makes it difficult for the chain to go backwards. Examples of such processes are binding of chaperonins, glycosylation, and/or chain folding. The propulsion mechanism of the intracellular pathogen Listeria monocytogenes is another example of a process that works, they believe, by ratcheted Brownian motion. This bacterium drives itself by building a tail of cross-linked actin filaments. They propose to model this process by simulating the coupled dynamics of tail assembly and the Brownian motion of the bacterium.