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Faculty
 Charles
Wolgemuth
Assistant Professor of Cell Biology
cwolgemuth@uchc.edu
Areas of Interest:
Computational Biology and Biophysics:
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.
Lab Rotation Projects:
1. How do bacteria maintain their form? We are currently engaged
in
a number of projects that use fluorescent confocal imaging to study how
cytoskeletal proteins influence the shapes of bacteria.
2. How do eukaryotic cells crawl? We have projects going that
study
the mechanics and regulation of cell crawling using C. elegans sperm as
our model system.
3. In addition, in conjunction with the experiments, we also
build mathematical and computer models to explore the physics and
biochemistry underlying cell form and motion.
Selected Publications:
S.C. Basu, C.W. Wolgemuth, and P. Campagnola. 2004. Measurement of
Anomolous Diffusing Dyes within Protein Structures Fabricated via
Multiphoton Excitation using Fluorescence Recovery after Photobleaching.
Biophys. J. (submitted).
C.W. Wolgemuth, A. Mogilner and G.Oster. 2004. The Hydration Dynamics
of Polyelectrolyte Gels with Applications to Drug Delivery and Cell
Motility. Eur. Biophys. J., 33: 146-158.
C.W. Wolgemuth, R.E. Goldstein, and T.R. Powers. 2004. Dynamic
Supercoiling Bifurcations of Growing Elastic Filaments. Physica D
190(3-4): 266-289.
C.W. Wolgemuth and G.Oster. 2004. The Junctional Pore Complex and the
Propulsion of Bacterial Cells. J. Mol. Microbiol. Biotechnol. 7: 72-77.
C.W. Wolgemuth, O. Igoshin, and G.Oster. 2003. The Motility of
Mollicutes. Biophys. J. 85: 828-842.
C. Wolgemuth, E. Hoiczyk, D. Kaiser and G. Oster. 2002. How
Myxobacteria Glide. Curr. Biol., 12(5): 369-377.
N.H. Mendelson, 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.
R.E. Goldstein, A. Goriely, G. Huber and C.W. Wolgemuth. 2000.
Bistable Helices. Phys. Rev. Lett., 84(7): 1631-1634.
C.W. Wolgemtuh, T.R. Powers and R.E. Goldstein. 2000. Twirling and
Whirling: Viscous dynamics of rotating elastica. Phys. Rev. Lett.,
84(7): 1623-1626. |
