title: Rat airway smooth muscle cell during actin modulation: rheology and glassy dynamics.
abstract: Although changes of cytoskeleton (CSK) stiffness and friction can be induced by diverse interventions, all mechanical changes reported to date can be scaled onto master relationships that appear to be universal. To assess the limits of the applicability of those master relationships, we focused in the present study on actin and used a panel of actin-manipulating drugs that is much wider than any used previously. We focused on the cultured rat airway smooth muscle (ASM) cell as a model system. Cells were treated with agents that directly modulate the polymerization (jasplakinolide, cytochalasin D, and latrunculin A), branching (genistein), and cross linking (phallacidin and phalloidin oleate) of the actin lattice. Contractile (serotonin, 5-HT) and relaxing (dibutyryl adenosine 3',5'-cyclic monophosphate, DBcAMP) agonists and a myosin inhibitor (ML-7) were also tested for comparison, because these agents may change the structure of actin indirectly. Using optical magnetic twisting cytometry, we measured elastic and frictional moduli before and after treatment with each agent. Stiffness increased with frequency as a weak power law, and changes of friction paralleled those of stiffness until they approached a Newtonian viscous limit. Despite large differences in the mechanism of action among the interventions, all data collapsed onto master curves that depended on a single parameter. In the context of soft glassy systems, that parameter would correspond to an effective temperature of the cytoskeletal matrix and reflect the effects of molecular crowding and associated molecular trapping. These master relationships demonstrate that when the mechanical properties of the cell change, they are constrained to do so along a special trajectory. Because mechanical characteristics of the cell shadow underlying molecular events, these results imply special constraints on the protein-protein interactions that dominate CSK mechanical properties.
authors.affiliation: Harvard School of Public Health, Bldg. 1, Rm. 317, 665 Huntington Ave., Boston, MA 02115-6021, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Laudadio
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Millet
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
authors.forename: Steven S
authors.initials: SS
authors.lastname: An
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
mesh_terms: D000199:Actins / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001696:Biomechanical Phenomena; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010590:Phalloidine / Q000494:pharmacology; D051381:Rats; D012212:Rheology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014132:Trachea / Q000166:cytology
chemical_list: D000199:Actins; D001381:Azepines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003432:Cross-Linking Reagents; D009281:Naphthalenes; D010456:Peptides, Cyclic; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D053778:Thiazolidines; C070571:ML 7; D010590:Phalloidine; D015638:Cytochalasin D; C017613:phallacidin; D012701:Serotonin; D003994:Bucladesine; D019833:Genistein; D009218:Myosins; C037067:latrunculin A