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. |
