Michael Sheetz

National University of Singapore, Singapore

Local Pinching Controls Molecular-Level Rigidity Sensing
Abstract No. : PL_07
Date & Time : Dec. 9 (Wed), 12:00-12:45
Place : Ballroom 1
Name : Michael Sheetz
Affiliation : National University of Singapore
Chair : Seok-Cheol Hong (Korea Univ.)
Abstract:Matrix rigidity is an important physical aspect of cell microenvironments;however, themechanismby which cells test substrate rigidity is not clear. Submicron pillar studies indicatethat cells may sense rigidity by measuring the forcesrequired 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 tropomyosin2.1 to sense rigidity and block growth on soft surfaces (Wolfenson et al., Nat Cell Bio. In Press).Tropomyosin2.1 is low in most metastatic cells and restoration of normal levels blocks transformation whereas knockdown in MCF-10A non-transformed cells causes them to become transformed.In addition, two tyrosine kinases involved in cancer progression, AXL and ROR2, are part of the contractile units and control distance and time of contractions to modify rigidity sensing, respectively (Yang et al., submitted). 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.