title: Filamin A is essential for active cell stiffening but not passive stiffening under external force.
abstract: The material properties of a cell determine how mechanical forces are transmitted through and sensed by that cell. Some types of cells stiffen passively under large external forces, but they can also alter their own stiffness in response to the local mechanical environment or biochemical cues. Here we show that the actin-binding protein filamin A is essential for the active stiffening of cells plated on collagen-coated substrates. This appears to be due to a diminished capability to build up large internal contractile stresses in the absence of filamin A. To show this, we compare the material properties and contractility of two human melanoma cell lines that differ in filamin A expression. The filamin A-deficient M2 cells are softer than the filamin A-replete A7 cells, and exert much smaller contractile stresses on the substratum, even though the M2 cells have similar levels of phosphorylated myosin II light chain and only somewhat diminished adhesion strength. In contrast to A7 cells, the stiffness and contractility of M2 cells are insensitive to either myosin-inhibiting drugs or the stiffness of the substratum. Surprisingly, however, filamin A is not required for passive stiffening under large external forces.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Kasza
authors.forename: F
authors.initials: F
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.forename: P
authors.initials: P
authors.lastname: Kollmannsberger
authors.forename: N
authors.initials: N
authors.lastname: Bonakdar
authors.forename: B
authors.initials: B
authors.lastname: Fabry
authors.forename: T P
authors.initials: TP
authors.lastname: Stossel
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: D A
authors.initials: DA
authors.lastname: Weitz
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects; D064448:Filamins; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D010766:Phosphorylation; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D003285:Contractile Proteins; D064448:Filamins; D006576:Heterocyclic Compounds, 4 or More Rings; D008840:Microfilament Proteins; D018994:Myosin Light Chains; C472645:blebbistatin; D024462:Myosin Type II