Mechanochemical Signaling Directs Cell State:
a Mechanics of Materials Foundation for Cell Biology
Mr. Adam J. Engler
Ph.D. Candidate
Advisor: Dr. Dennis Discher
Department of Mechanical Engineering
University of Pennsylvania
Abstract
Many different cells respond to substrate elasticity
as sensitively as more well studied soluble or immobilized
ligands, yet mechanisms by which mechanical cues are transduced
to cells have been far less explored. Sufficient substrate
stiffness, i.e. – Young’s Modulus E, appears
important to anchorage-dependent, contractile cells, relying
on finite resistance to cell-generated forces to induce
outside-in mechanical signals and maintain cell function.
Muscle cells, in particular, transmit large actomyosin contractions
to surrounding extracellular matrix (ECM), appearing mechanochemically
sensitive very early as cell adhesion depends on substrate
compliance and adhesive ligand density; limited spreading
on soft gels (E = 1kPa) is surprisingly insensitive to adhesive
ligand density. On rigid matrices or substrates, cells produce
isometric contractile efforts not conducive to cell function;
in contrast, a more compliant matrix, i.e. – a collagen
or polyacrylamide gel, permits cell contractions. Thus,
longer-term cultures indicate that muscle cell striation
and function is sensitive to substrate compliance, with
an intermediate stiffness similar to passive muscle (EMuscleCell
~ 12kPa) being most favorable. Remarkably, mesenchymal stem
cell differentiation also appears mechanosensitive, with
cells adopting a myoblast-like elongation and expressing
muscle cell markers on substrates only near EMuscleCell,
while on substrates near EBoneCell, cells have a polygonal
morphology and express bone cell markers. Incomplete expression
by mechanosensing is augmented by chemical stimuli thus
inducing full differentiation; chemical or physical stimulus
alone cannot, indicating a coupled effect.
Overall, our data implies and will demonstrate
that, in addition to soluble or immobilized ligands, tissue
and/or matrix mechanical and structure properties are critical
for cell development and therapies.
Thursday, September 22nd
337 Towne Bldg.
2:00 – 3:00 p.m.
