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.
