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Mechanobiology of Disease
Poster Abstracts
70
79-POS
Board 79
Force Generation in Initial Cell-Matrix Interaction through E-Cadherin Mediated Cell
Adhesion
Yi An Yang
1
, Emmanuelle Nguyen
1
, Felix M. Margadant
1
, Shuaimin Liu
2
, Benoit Ladoux
1,3
,
Michael P. Sheetz
1,4
.
1
Mechanobiology Institute, Singapore, Singapore,
4
Columbia University, New York, NY,
USA.
2
Columbia University, New York, NY, USA,
3
Centre National de la Recherche
Scientifique UMR 7592 and Université Paris Diderot, Paris, France,
In our research we aimed at understanding how cells respond to matrix stiffness through E-
cadherin adhesion. Previous research have revealed that cells were able to sense varying
extracellular environmental stiffness through cadherin mediated adhesion, but detailed
mechanism remained largely obscure. Through utilizing sub-micron size pillar arrays, made with
PDMS and surface functionalized with E-cadherin, we were able to mimic continuous surface
that allow cell to form cadherin clusters, and record force generated by cell against substrate. We
discovered that cells would generate local contraction in their initial contact with pillar substrate,
with myosin light chain phosphorylation observed in between pillars, where cells were anchored
upon through E-cadherin. Cells pulled pillar through these local contractile units to a constant
maximum distance, which was independent of pillar rigidity but dependent of pillar spacing.
These results indicated that cells were able to generate force actively based upon E-cadherin
mediated adhesion, while contraction length remained constant regardless of stiffness change,
allowing differential force input of cell according to substrate stiffness. Such force generation
event resembled integrin mediated local contraction in fibroblast that initiated rigidity sensing,
and could be involved in cadherin mediated rigidity sensing and adhesion maturation.