title: Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices.
abstract: Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied by local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal- and spatial-resolution tracking of contractile forces by plating cells on sub-micrometre elastomeric pillars. We found that actomyosin-based sarcomere-like contractile units (CUs) simultaneously moved opposing pillars in net steps of ∼2.5 nm, independent of rigidity. What correlated with rigidity was the number of steps taken to reach a force level that activated recruitment of α-actinin to the CUs. When we removed actomyosin restriction by depleting tropomyosin 2.1, we observed larger steps and higher forces that resulted in aberrant rigidity sensing and growth of non-transformed cells on soft matrices. Thus, we conclude that tropomyosin 2.1 acts as a suppressor of growth on soft matrices by supporting proper rigidity sensing.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.|The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.
authors.forename: Haguy
authors.initials: H
authors.lastname: Wolfenson
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.|The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.|Department of Chemical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Meacci
authors.affiliation: The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.|Department of Mechanical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: Shuaimin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Chemical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Stachowiak
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.|The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Iskratsch
authors.affiliation: The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.|Department of Mechanical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: Saba
authors.initials: S
authors.lastname: Ghassemi
authors.affiliation: Institute for Bioengineering of Catalonia and University of Barcelona, Barcelona 08028, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Roca-Cusachs
authors.affiliation: Department of Chemical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: O'Shaughnessy
authors.affiliation: The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.|Department of Mechanical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hone
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.|The Nanomedicine Center for Mechanobiology Directing the Immune Response, Columbia University, New York, New York 10027, USA.|Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D008841:Actin Cytoskeleton; D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D012518:Sarcomeres / Q000378:metabolism*; D013314:Stress, Mechanical; D014335:Tropomyosin / Q000378:metabolism*
chemical_list: D000199:Actins; C518659:TPM2 protein, human; D014335:Tropomyosin; D000205:Actomyosin