α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions.
During spreading and migration, the leading edges of cells undergo periodic protrusion-retraction cycles. The functional purpose of these cycles is unclear. Here, using submicrometer polydimethylsiloxane pillars as substrates for cell spreading, we show that periodic edge retractions coincide with peak forces produced by local contractile units (CUs) that assemble and disassemble along the cell edge to test matrix rigidity. We find that, whereas actin rearward flow produces a relatively constant force inward, the peak of local contractile forces by CUs scales with rigidity. The cytoskeletal protein α-actinin is shared between these two force-producing systems. It initially localizes to the CUs and subsequently moves inward with the actin flow. Knockdown of α-actinin causes aberrant rigidity sensing, loss of CUs, loss of protrusion-retraction cycles, and, surprisingly, enables the cells to proliferate on soft matrices. We present a model based on these results in which local CUs drive rigidity sensing and adhesion formation.
Department of Biological Sciences, Columbia University, New York, NY 10027 giovannimeacci@gmail.com hw2385@columbia.edu ms2001@columbia.edu.|Department of Chemical Engineering, Columbia University, New York, NY 10027.
Giovanni
G
Meacci
Department of Biological Sciences, Columbia University, New York, NY 10027 giovannimeacci@gmail.com hw2385@columbia.edu ms2001@columbia.edu.
Haguy
H
Wolfenson
Department of Mechanical Engineering, Columbia University, New York, NY 10027.
Shuaimin
S
Liu
Department of Chemical Engineering, Columbia University, New York, NY 10027.
Matthew R
MR
Stachowiak
Department of Biological Sciences, Columbia University, New York, NY 10027.|Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Thomas
T
Iskratsch
Department of Mechanical Engineering, Columbia University, New York, NY 10027.
Anurag
A
Mathur
Department of Mechanical Engineering, Columbia University, New York, NY 10027.
Saba
S
Ghassemi
Department of Biological Sciences, Columbia University, New York, NY 10027.|Mechanobiology Institute, National University of Singapore, Singapore, 117411.
Nils
N
Gauthier
Department of Biomedical Engineering, Columbia University, New York, NY 10027.
Erdem
E
Tabdanov
Department of Biological Sciences, Columbia University, New York, NY 10027.
James
J
Lohner
Department of Mechanical Engineering, Columbia University, New York, NY 10027.
Alexander
A
Gondarenko
Department of Biological Sciences, Columbia University, New York, NY 10027.
Ashok C
AC
Chander
Department of Biological Sciences, Columbia University, New York, NY 10027.|Institute for Bioengineering of Catalonia and University of Barcelona, 08028 Barcelona, Spain.
Pere
P
Roca-Cusachs
Department of Chemical Engineering, Columbia University, New York, NY 10027.
Ben
B
O'Shaughnessy
Department of Mechanical Engineering, Columbia University, New York, NY 10027.
James
J
Hone
Department of Biological Sciences, Columbia University, New York, NY 10027 giovannimeacci@gmail.com hw2385@columbia.edu ms2001@columbia.edu.|Mechanobiology Institute, National University of Singapore, Singapore, 117411.
Michael P
MP
Sheetz
D000185:Actinin / Q000378:metabolism* / Q000502:physiology; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction; D011554:Pseudopodia / Q000378:metabolism
D000199:Actins; D000185:Actinin