title: Calcium signaling is gated by a mechanical threshold in three-dimensional environments.
abstract: Cells interpret their mechanical environment using diverse signaling pathways that affect complex phenotypes. These pathways often interact with ubiquitous 2(nd)-messengers such as calcium. Understanding mechanically-induced calcium signaling is especially important in fibroblasts, cells that exist in three-dimensional fibrous matrices, sense their mechanical environment, and remodel tissue morphology. Here, we examined calcium signaling in fibroblasts using a minimal-profile, three-dimensional (MP3D) mechanical assay system, and compared responses to those elicited by conventional, two-dimensional magnetic tensile cytometry and substratum stretching. Using the MP3D system, we observed robust mechanically-induced calcium responses that could not be recreated using either two-dimensional technique. Furthermore, we used the MP3D system to identify a critical displacement threshold governing an all-or-nothing mechanically-induced calcium response. We believe these findings significantly increase our understanding of the critical role of calcium signaling in cells in three-dimensional environments with broad implications in development and disease.
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Ruder
authors.forename: Erica D
authors.initials: ED
authors.lastname: Pratt
authors.forename: Nailah Z D
authors.initials: NZ
authors.lastname: Brandy
authors.forename: David A
authors.initials: DA
authors.lastname: LaVan
authors.forename: Philip R
authors.initials: PR
authors.lastname: LeDuc
authors.forename: James F
authors.initials: JF
authors.lastname: Antaki
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D057054:Molecular Imaging; D041681:NIH 3T3 Cells; D010812:Physical Stimulation