2010-ASCB-Press-Book - page 11

T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
News from
The American Society
for Cell Biology
50th Annual Meeting
Philadelphia, PA
December 11–15, 2010
How deeply do cells feel?
10:00 am, U.S. Eastern Time
Monday, December 13, 2010
Amnon Buxboim
Biophysical Engineering Lab,
129 Towne Bldg.
University of Pennsylvania
Philadelphia, PA 19104-6315
Author presents
Monday, December 13, 2010
1:00 pm–2:30 pm
Session: Extracellular Matrix
and Signaling I
Exhibit Halls A/B/C
Program: 1361
Board: B660
How Deeply Cells Feel: Regula-
tion of Cellular Organization
and Differentiation by Matrix
A. Buxboim, D.E. Discher
Physics and Astronomy,
University of Pennsylvania,
Philadelphia, PA
E.C. Eckels, D.E. Discher
Chemical and Biomolecular
Engineering, University of
Pennsylvania, Philadelphia, PA
D.E. Discher
Cell and Molecular Biology
Graduate Group, University of
Pennsylvania, Philadelphia, PA
This work was supported by NIH
R01-HL062352, R21-AR056128,
P01-DK032094, Human Frontier
Sciences Program Grant, and
NSF–NSEC NanoBio Interface
Like the fairy princess on the
mattress pile, stem cells can feel
what’s under the bedding
ells lack eyes to see and ears to
hear, but they seem to have an
acute sense of touch. As tissue
cells adhere to a soft natural extracellular
matrix, they pull and deform the surface,
allowing them to feel below the surface
of their new bedding. But how deeply can
cells feel? The question seems like that
posed in the fairy tale “The Princess and
the Pea,” when only a true princess could
feel a hard pea placed under a stack of
Amnon Buxboim, Dennis Discher,
and colleagues at the University of Penn-
sylvania don’t work with peas and mat-
tresses but with cultured adherent stem
cells grown on microfilms of controlled
thickness and elasticity that are, in turn,
bonded to rigid glass. The researchers
predicted that thickness and stiffness
of the microfilm would greatly affect
the form of cells grown on
top. The researchers used
naive mesenchymal stem
cells (MSCs) as prototypical
adherent cells. These MSCs
are particularly sensitive to
microenvironmental factors
such as elasticity or hard-
ness as they differentiate into
cells of specific tissue types.
Controlling or predicting how
stem cells will differentiate is
a vital issue for bioengineer-
ing artificial tissue and in
stem cell medicine.
Matrix elasticity is a cru-
cial variable because tissue
microenvironments exhibit a
hierarchy in stiffness: Brain is
softer than muscle, muscle is
softer than cartilage matrix, and cartilage
matrix is softer than precalcified bone.
The Penn researchers plated their MSCs
onto the different matrices and deployed
a range of methods to document sig-
nificant differences between stem cells
grown on thin films versus thick films. The
teammeasured cell shape by confocal
microscopy and microelasticity by atomic
force microscopy. They analyzed cellular
responses in terms of morphology while
mapping cytoskeletal organization by
using nonmuscle myosin assembly. The
researchers evaluated changes in gene ex-
pression by using DNA microarray–based
transcriptional analysis of the genome.
By these and other measures, the
researchers concluded that cells can
feel up to several microns into compli-
ant matrices. The stiffer the surface, the
shallower cells could feel; the softer, the
deeper. Ultimately, cells feel the differ-
ence between stiff and soft or thick and
thin surroundings, regardless of whether
they are of royal descent.
To understand how deeply cells feel, adult-derived stem cells (above)
were grown on soft matrices of different thickness on top of rigid
glass for comparison to cell growth on plastic. These cells are
especially sensitive to their microenvironment. Both cell and nuclear
morphology as well as gene expression analyses (right) show that
cells can feel rigid substrates beneath them even if there is an inter-
vening soft matrix. These early changes in expression of key structural
genes of the nucleus (left) and cytoskeleton (middle) further show
that cells reprogram their structures as they initiate differentiation.
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