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Living cells are complex machines. Although molecular biology and biochemistry have elucidated a large number of the processes that occur within cells, the physical interplay between a cell and itself or its environment is often overlooked. Recently, with new experimental techniques that can probe subcellular motions and forces, a more complete picture of cellular biology is emerging that shows that the mechanisms underlying cellular processes rely on a complex interaction between the genetic blueprint of the cell and its physical makeup and environment. One such experiment found that the left-right asymmetry in mammals is a consequence of a fluid dynamic instability caused by the rotation of filaments in the developing embryo. This type of evidence strongly suggests that a complete understanding of cellular biology is not possible without physical models that suggest mechanisms by which cells function. My research program focuses on the application of physics, such as elasticity, hydrodynamics and statistical mechanics, to describe cellular morphology, motility and growth. Currently I am working on projects that fall under two classifications and are described below. Elastic filaments are common building blocks for cells. Alone or in combination with other filaments, they can provide structural integrity while maintaining a necessary degree of flexibility. Bacteria, some of the simplest living organisms, have found many uses for elastic filaments. Two such examples are the flagellum, a rotary oar that propels most swimming bacteria, and mbl, a recently discovered protein that helps maintain form in cylindrical bacteria. My past research dealt with describing the dynamics of elastic filaments in viscous environments and was used to study the dynamics of morphology changes in bacterial flagella and also the supercoiling motions of Bacillus subtilis. I am currently working on projects to understand the morphology and swimming of spirochete bacteria, unique helically shaped cells whose flagella are encased within their cell wall. By rotating these flagella, spirochetes induce shape changes and rotation in their cell wall that propels them through viscous and gelatinous environments. By treating the flagella and the cell wall as coupled elastic filaments, I hope to explain the morphological differences between flagellated and unflagellated spirochetes as well as understanding the mechanism by which rotation of the flagella leads to propulsion. Eukaryotic cells are quite different than bacteria. Though some eukaryotic cells swim, a number of motile cells crawl, such as white blood cells and fibroblasts, which are responsible for wound healing. This crawling behavior is accomplished through a complex process requiring adhesion to a surface, extension at the front end of the cell and retraction at the back end of the cell. In most eukaryotic cells, extension and retraction are accomplished by polymerization and depolymerization of actin. Actin is a filamentous protein that forms multi-filament bundles. These bundles, when surrounded by fluid, constitute a gel, a polymer mesh immersed in a fluid solvent. I have recently developed a physical theory that describes the dynamics of charged and uncharged gels. Using this theory, I created a model describing a mechanism for gliding motility in bacteria. This model is currently the most accepted mechanism for A-motility in Myxococcus xanthus as well as gliding in cyanobacteria. I currently plan to use this gel theory to explain crawling motions in eukaryotic cells. Some questions that can be addressed are: How does actin bundling affect the material parameters of the gel and the propulsive force? What polymerization mechanisms produce the observed lamellipod extension? These processes will be explored using the gel equations previously derived in conjunction with adhesion and depolymerization. As well, the fluid flow inside of the cell can be theoretically predicted for the first time.
Selected Publications Wolgemuth, C.W., T.R. Powers and R.E. Goldstein. 2000. Rotating Elastic Filaments. Phys. Rev. Lett. 84(7):1623-1626. Mendelson N.H., J.A. Sarlls, C.W. Wolgemuth and R.E. Goldstein. 2000. Chiral Self-Propulsion of Growing Bacterial Macrofibers on a Solid Surface. Phys. Rev. Lett 84(7):1627-1630. Goldstein R.E., A. Goriely, G. Huber, and C.W. Wolgemuth. 2000. Bistable Helices. Phys. Rev. Lett. 84(7):1631-1634. Wolgemuth C, E. Hoiczyk, D. Kaiser and G. Oster. 2002. How Myxobacteria Glide. Curr. Biol. 12(5):369-277. Wolgemuth C.W., O. Igoshin , and G. Oster. 2003. The Motility of Mollicutes. Biophys J. 85:828-842. Wolgemuth C.W., R.E. Goldstein, and T.R. Powers. 2004. Dynamic Supercoiling Bifurcations of Growing Elastic Filaments. Physica D 190: 266-289. Wolgemuth CW, A. Mogilner, and G. Oster. 2004. The Hydration Dynamics of Polyelectrolyte Gels with Applications to Cell Motility and Drug Delivery. Eur. Biophys. J. 33: 146-158. Wolgemuth CW, and G. Oster. 2004. The Junctional Pore Complex and the Propulsion of Bacterial Cells. J. Mol. Microbiol. Biotech. 7: 72-77. Basu, SC, CW Wolgemuth, and P Campagnola. 2004. Measurement of Anomalous Diffusing Dyes within Protein Structures Fabricated via Multiphoton Excitation using Fluorescence Recovery after Photobleaching. Biomacromol. 5: 2347-2357. Tuval, I, L Cisneros, C Dombrowski, CW Wolgemuth, JO Kessler, and RE Goldstein. Bacterial Swimming and Oxygen Transport Near Contact Lines. 2005. Proc. Natl. Acad. Sci USA 102: 2277-2282. Wolgemuth, CW, L Miao, O Vanderlinde, T Roberts, and G Oster. 2005. MSP Dynamics Drives Nematode Sperm Locomotion. Biophys. J. 88: 2462-2471. Cogan, NG, and CW Wolgemuth. 2005. Pattern Formation by Bacteria-driven Flow. Biophys. J. 88: 2525-2529. Wolgemuth, CW. 2005. Force and Flexibility of Flailing Myxobacteria. Biophys. J. 89: 945-950. Wolgemuth, CW, Y. Inclan, J. Quan, G. Oster, and M.A.R. Koehl. 2005. How to Make a Spiral Bacterium. Phys. Biol. 2: 189-199. Wolgemuth, CW. 2005. Lamellipodial Contractions during Crawling and Spreading. Biophys. J. 89: 1643-1649. Wolgemuth, CW, and S.X. Sun. 2006. The Elasticity of Alpha-helical Coiled-coils. Proc. Natl. Acad. Sci. USA (submitted). Wolgemuth, CW, N.W. Charon, S.F. Goldstein, and R.E. Goldstein. 2005. The Flagellar Cytoskeleton of the Spirochetes. J. Mol. Microbiol. Biotechnol. (submitted). |
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