|
| |
|
|
|
Richard B. Dickinson
Professor
Ph.D., 1992, University of Minnesota
Cellular engineering
Cell adhesion
Cell migration
Molecular Motors
Mathematical Biology
|
|
Brief Description of
Current Research
We apply engineering principles to study the behavior of living
cells or other small-scale biological systems (e.g.
bionanotechnological systems). That is, we use a combination of
mathematical modeling, quantitative experimentation, together with
the tools of molecular cell biology to better understand the
relationship between cell function and the physical and molecular
properties of cells and their surroundings. The field is often
called cellular bioengineering or cellular engineering.
We are studying the mechanisms of actin-based cell motility using a
combination of mathematical modeling, small-scale biophysical
measurements, and molecular cell biology. In collaboration with faculty
in the College of Medicine, we have discovered and are investigating a
new class of biomolecular motors, called “filament end-tracking motors”,
that we believe are responsible for force generation by actin
polymerization, which drives cell protrusions during cell crawling, as
well as the intracellular transport of vesicles and some invasive
pathogenic microorganisms such as Listeria monocytogenes. This
mechanism has wide-ranging relevance in cell biology and microbiology,
as it has been cited by others to explain plasmid segregation in
prokaryotes by polymerization of actin homologs, and to explain the
force-generating properties by end-tracking proteins called formins in
yeast-cell division.
In addition to fundamental studies, we are currently working to
exploit filament end-tracking motors for transporting biomolecules and
microorganisms in biosensing devices. We are developing nanoscale
actuators and molecular shuttles consisting of surface-tethered
biomotors propelled by actin polymerization on patterned and
microfabricated substrata. This system will serve as an alternative to
microfluidics or electric fields to transport and sort these species in
“lab-on-a-chip” applications.
Another major area of focus is cell adhesion, which is relevant to
applications such as the design of biomaterials for biomedical implants,
cell carriers for bioreactors in the bioprocessing industry, and filters
to remove microorganisms in water purification. Our goal is to develop
models that can predict the probability and strength of adhesion as a
function of measurable molecular and physical properties of the cell and
substratum. In addition to “macroscopic” surface properties such as
hydrophobicity and surface charge, we are interested in the role of
specific interactions between cell surface molecules and the
substratum. We have developed a novel force-measurement instrument
involving an optical trap force-transducer and evanescent wave light
scattering to probe dynamic interaction forces between a single microbe
and a surface with nanometer resolution and a sensitivity of tens of
femptoNewtons. Our technique was the first to measure the
force-distance profile between a single bacterium and a substratum.
Major equipment available in our laboratory include an Automated
Video-microscopy System, an optically-trapped particle tracking system
for dynamic force-measurements, a Nikon Three-Laser Total Internal
Reflection Fluorescence Microscope, and comprehensive cell-culture
facilities.
Selected Publications
- “Direct evaluation of DLVO theory for predicting long-range forces
between a yeast cell and a surface”, Sharp, J., and R. B. Dickinson,
Langmuir (to appear, 2005).
- "Listeria's Right-Handed Helical Rocket-tail Trajectories:
Mechanistic Implications for Force Generation in Actin-Based Motility",
Zeile, W. L., Zhang, F, Dickinson, R. B., and D. L. Purich, Cell
Motil Cytoskeleton, Vol. 60 (2), 121-8. (2005).
- "Force Generation by Cytoskeletal Filament End-Tracking Proteins."
Biophysical Journal, Dickinson, R. B., Caro. L. and D. L. Purich,
Vol. 87, 2838-2854 (2004).
- "Kinetic Analysis of the Attachment of a Biological Particle to a
Surface by Macromolecular Binding", Ma, H. and R. B. Dickinson, J
Theor. Biol., Vol. 226, 237-250 (2004).
- "Direct measurement of colloidal forces between a single bacterium
and a surface", Klein, J., A. R. Clapp, and R. B. Dickinson, J.
Colloid & Interface Sci., Vol. 261, 379-385 (2003).
- “Kinetics and forces of adhesion for a pair of capsular/unencapsulated
Staphylococcus mutant strains”, Prince, J. and R. B. Dickinson,
Langmuir, Vol. 19 (1), 154-159, (2003)
- "A clamped-filament elongation model for actin-based motors",
Dickinson, R. B. and D. L. Purich, Biophysical J., Vol. 85,
605-617 (2002).
- "Direct measurement of static and dynamic forces between a colloidal
particle and a surface using a single-beam gradient optical trap and
evanescent wave light scattering”, Clapp, A. R. and R. B. Dickinson,
Langmuir, Vol. 17, 2182-91 (2001).
|
