Mathematical Sciences: Mathematical Models in Cellular & Developmental Biology

研究者和他的同事通过数学建模和计算机模拟研究了几种与细胞和细胞器运动的机械化学有关的现象。特别是，他们关注的是有偏随机运动在两个组织层次上创造秩序的作用。在细胞/组织水平上，他们研究了随机细胞运动如何通过边界抑制和细胞间通信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运动现象，这些现象似乎通过利用化学键能来棘轮分子的组装和拆卸，从随机热运动中提取功。本研究旨在研究细胞在形态发生过程中如何运动和改变形状，以及大分子如何跨细胞膜运输的基本问题。这些问题对于基本的理解是重要的，并且对诸如伤口愈合和组织发育等问题也有影响。在核糖体上的蛋白质合成过程中和合成后，新生多肽链必须穿过细胞膜进入细胞内腔室，如内质网和线粒体。这是如何完成的是一个谜，因为它似乎是在缺乏代谢能量来源的情况下进行的，比如核苷酸水解。研究人员提出了一种机制来解释这一过程，该机制基于氨基酸链的热运动可以被任何使链难以向后移动的过程所偏倚的想法。这类过程的例子有伴侣蛋白结合、糖基化和/或链折叠。他们认为，细胞内病原体单核增生李斯特菌的推进机制是通过棘轮布朗运动起作用的另一个例子。这种细菌通过建立一个交联的肌动蛋白丝的尾巴来驱动自己。他们建议通过模拟细菌尾部装配的耦合动力学和布朗运动来模拟这一过程。

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.