title: Actin cap associated focal adhesions and their distinct role in cellular mechanosensing.
abstract: The ability for cells to sense and adapt to different physical microenvironments plays a critical role in development, immune responses, and cancer metastasis. Here we identify a small subset of focal adhesions that terminate fibers in the actin cap, a highly ordered filamentous actin structure that is anchored to the top of the nucleus by the LINC complexes; these differ from conventional focal adhesions in morphology, subcellular organization, movements, turnover dynamics, and response to biochemical stimuli. Actin cap associated focal adhesions (ACAFAs) dominate cell mechanosensing over a wide range of matrix stiffness, an ACAFA-specific function regulated by actomyosin contractility in the actin cap, while conventional focal adhesions are restrictively involved in mechanosensing for extremely soft substrates. These results establish the perinuclear actin cap and associated ACAFAs as major mediators of cellular mechanosensing and a critical element of the physical pathway that transduce mechanical cues all the way to the nucleus.
authors.affiliation: Johns Hopkins Physical Sciences in Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Dong-Hwee
authors.initials: DH
authors.lastname: Kim
authors.forename: Shyam B
authors.initials: SB
authors.lastname: Khatau
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Feng
authors.forename: Sam
authors.initials: S
authors.lastname: Walcott
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Longmore
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
mesh_terms: D051344:Actin Capping Proteins / Q000378:metabolism*; D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D024462:Myosin Type II / Q000378:metabolism
chemical_list: D051344:Actin Capping Proteins; D000199:Actins; D000185:Actinin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D024462:Myosin Type II