From the Physiology Program, Department of Environmental Health, Harvard
School of Public Health, Boston, Mass.
Correspondence to Dr Ning Wang, Physiology Program, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail nwang{at}hsph.harvard.edu
Abstract
Abstract—Mechanical properties of
the cells are important in controlling cell shape, cell migration, and
other functions. To understand how cytoskeletal (CSK) filaments
interact with one another mechanically, mechanical properties of
adherent endothelial cells were analyzed after
treatment with CSK-disrupting drugs. CSK stiffness (the ratio of
applied stress to strain, a measure of cell resistance to shape
deformation), viscosity (an index of intracellular structural damping),
and permanent deformation (a measure of "plasticity") were measured
with magnetic twisting cytometry, by which rotational stress was
applied directly to integrin receptors with ferromagnetic beads coated
with RGD-containing peptide. Treatment with cytochalasin D, which
disrupts actin microfilaments inhibited stiffness by 50% and decreased
permanent deformation from 70% to 50% but had almost no effect on
viscosity. In contrast, nocodazole, a microtubule disrupter, had very
little effect on inhibition of CSK stiffness, decreased viscosity by
25%, and had no effects on permanent deformation.
Acrylamide, an intermediate filament disrupter, had little
effect on inhibition of CSK stiffness, little effect on viscosity, and
no effect on permanent deformation. Taxol, a drug that facilitates
microtubule polymerization, increased stiffness by 10%, increased
viscosity by 10%, and decreased permanent deformation from 70% to
50%. Combinations of cytochalasin D and nocodazole, cytochalasin D and
acrylamide, or all three drugs resulted in a synergistic
effect on inhibition of CSK stiffness and viscosity but not in
permanent deformation. Inhibition of oxidative metabolism
with potassium cyanide had no effects on stress-induced stiffening
response. Inhibition of tyrosine phosphatase with phenylarsine oxide
had no effect on stress-induced stiffening response. We conclude that
higher order mechanical interactions of CSK filaments are important in
determining the mechanical properties of the cell.
© 1998 American Heart Association, Inc.
Third Workshop on Structure and Function of Large Arteries: Part I
Mechanical Interactions Among Cytoskeletal Filaments
Key Words: microfilaments • microtubules • cytoskeleton • cytometry
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