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Mechanobiology of Disease
Tuesday Speaker Abstracts
9
Rigidity Sensing Contractions Inhibit Transformed Growth
Michael P. Sheetz
1,2
Bo Yang
1
, Haguy Wolfenson
2
, Zi Zhao Lieu
1
, Feroz M.Hameed
1
,
Alexander D. Bershadsky
1
1
Mechanobiology Institute, National University of Singapore, Singapore,
2
Department of
Biological Sciences, Columbia University, NY, USA
Matrix rigidity is an important physical aspect of cell microenvironments; however, the
mechanism by which cells test substrate rigidity is not clear. Submicron pillar studies indicate
that cells sense rigidity by measuring the forces required for local standard contractions at the
cell periphery (pinching activity) (Ghassemi et al., 2012. PNAS 109:5328). Recent observations
show that sarcomere-like units drive step-wise contractions that depend upon tropomyosin to
sense rigidity and block growth on soft surfaces (Wolfenson et al., 2016. Nat. Cell Bio. 18:33).
In addition, two tyrosine kinases involved in cancer progression are part of the contractile units
and control distance and time of contractions to modify rigidity sensing (Yang et al., 2016.
Nanoletters. In Press). Thus, we suggest that these tyrosine kinases affect adhesion-dependent
mechanosensitivity and consequently metastasis and morphology changes in development
through their regulation of local mechanosensory contractions by sarcomere-like units with
tropomyosin.