2005 APS March Meeting
Monday–Friday, March 21–25, 2005;
Los Angeles, CA
Session J7: Biological Microsystem Technologies Using Microfluidics and Integrated Circuits
11:15 AM–2:15 PM,
Tuesday, March 22, 2005
LACC
Room: 408B
Sponsoring
Unit:
DBP
Chair: Robert M. Westervelt, Harvard University
Abstract ID: BAPS.2005.MAR.J7.5
Abstract: J7.00005 : Biomagnetics and Cell-Based Biochips
1:39 PM–2:15 PM
Preview Abstract
Abstract
Author:
Donald Ingber
(Harvard Medical School/Children's Hospital)
This
presentation will review various micro- and nanotechnologies
that
we have
developed over the past decade in our efforts to manipulate and
probe living
cells. In early studies, we used magnetic micro-particles to
apply
controlled mechanical forces to surface membrane receptors. We
did this to
probe cellular mechanical properties, and to investigate the
molecular basis
of mechanotransduction -- how mechanical forces are transduced
into changes
in intracellular biochemistry. The magnetic beads were coated
with ligands
for adhesion receptors, such as synthetic RGD
(arginine-glycine-aspartate)
peptides or antibodies that bind to membrane integrin receptors.
Controlled
twisting (torque) or pulling (tension) forces were exerted on
the
integrin-bound beads using magnetic twisting or pulling
cytometry. To
investigate the cellular response to dynamic forces, and to
increase the
level of stress applied, an electromagnetic needle was developed
to apply a
temporally varying magnetic field controlled by a user-defined
solenoidal
current; the end of the needle also was electropolished to
produce a
nanoscale pole tip. Magnetic forces applied to integrin
receptors, but not
other cell-surface receptors, induced force-dependent
recruitment of
cytoskeletal linker (focal adhesion) proteins to the site of
bead
binding,
resulting in assembly and mechanical strengthening of the
adhesions. Stress
application to integrins also resulted in force-dependent
increases in cAMP
signaling and induction of gene transcription. These experiments
revealed
that integrins and the cytoskeleton play a central role in
cellular
mechanotransduction.studies in collaboration with George
Whitesides (Harvard
U.), we used microcontact printing techniques with self-
assembled
monolayers
of alkanethiols to microfabricate extracellular matrix-coated
adhesive
islands of defined size, shape, and position on the micrometer
scale. When
cells were plated on these islands, the spread to take on the
form of the
island. These studies revealed that cells can be switched
between
growth,
differentiation, and death (apoptosis) by varying the degree to
which a cell
physically can distend. When cells grown on islands with corners
(e.g.,
squares, triangles) were stimulated with motility factors, the
cells
preferentially extended new motile processes from the corner
regions,
whereas cells on circular islands showed no bias. These
findings
demonstrated that much of cell behavior is controlled through
physical
interactions between cells and their adhesive substrate, and
that
microfabrication methods may be useful for tissue engineering,
as
well as
creation of ``laboratories on a chip'' or biosensor devices that
incorporate
living mammalian cells. addition, in experiments with Bob
Westervelt and
Donhee Ham (Harvard U.), we have demonstrated the feasilibility
of using
microelectromagnetic circuits and CMOS technology to physically
pull cells
out from medium magnetically, and to move them in a directed
manner. This
approach may have great value for cell separation applications.
Finally,
with Whitesides group, we also demonstrated that microfluidics
technologies
may be used to deliver chemicals or probes to different regions
of the same
living cell under flow conditions. This provides a novel way to
create
chemical gradients at the subcellular scale and thereby probe
the
relation
between cell structure and function. We also are currently
exploring novel
uses of microfluidics technologies, including their application
for clinical
cell separation applications. Taken together,
this body of
his work clearly demonstrates the great value of microsystem
and
microfluidic approaches for the analysis and manipulation of
living cells.
These approaches may have great value, both for fundamental
scientific
research and for clinical applications.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2005.MAR.J7.5