title: Cell elasticity determines macrophage function.
abstract: Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America. npatel@bidmc.harvard.edu
authors.forename: Naimish R
authors.initials: NR
authors.lastname: Patel
authors.forename: Medhavi
authors.initials: M
authors.lastname: Bole
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hardin
authors.forename: Alvin T
authors.initials: AT
authors.lastname: Kho
authors.forename: Justin
authors.initials: J
authors.lastname: Mih
authors.forename: Linhong
authors.initials: L
authors.lastname: Deng
authors.forename: James
authors.initials: J
authors.lastname: Butler
authors.forename: Daniel
authors.initials: D
authors.lastname: Tschumperlin
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Krishnan
authors.forename: Henry
authors.initials: H
authors.lastname: Koziel
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004548:Elasticity / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D055503:Protein Multimerization / Q000187:drug effects; D059467:Transcriptome; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D020741:rho GTP-Binding Proteins