title: High resolution, large deformation 3D traction force microscopy.
abstract: Traction Force Microscopy (TFM) is a powerful approach for quantifying cell-material interactions that over the last two decades has contributed significantly to our understanding of cellular mechanosensing and mechanotransduction. In addition, recent advances in three-dimensional (3D) imaging and traction force analysis (3D TFM) have highlighted the significance of the third dimension in influencing various cellular processes. Yet irrespective of dimensionality, almost all TFM approaches have relied on a linear elastic theory framework to calculate cell surface tractions. Here we present a new high resolution 3D TFM algorithm which utilizes a large deformation formulation to quantify cellular displacement fields with unprecedented resolution. The results feature some of the first experimental evidence that cells are indeed capable of exerting large material deformations, which require the formulation of a new theoretical TFM framework to accurately calculate the traction forces. Based on our previous 3D TFM technique, we reformulate our approach to accurately account for large material deformation and quantitatively contrast and compare both linear and large deformation frameworks as a function of the applied cell deformation. Particular attention is paid in estimating the accuracy penalty associated with utilizing a traditional linear elastic approach in the presence of large deformation gradients.
authors.affiliation: School of Engineering, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Jennet
authors.initials: J
authors.lastname: Toyjanova
authors.affiliation: School of Engineering, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Eyal
authors.initials: E
authors.lastname: Bar-Kochba
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Center of Biomedical Engineering, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Cristina
authors.initials: C
authors.lastname: López-Fagundo
authors.affiliation: Department of Surgery, Rhode Island Hospital, Providence, Rhode Island, United States of America; The Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reichner
authors.affiliation: School of Engineering, Brown University, Providence, Rhode Island, United States of America; Department of Molecular Pharmacology, Physiology and Biotechnology, Center of Biomedical Engineering, Brown University, Providence, Rhode Island, United States of America; Brown Institute for Brain Science, Providence, Rhode Island, United States of America.
authors.forename: Diane
authors.initials: D
authors.lastname: Hoffman-Kim
authors.affiliation: School of Engineering, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Franck
mesh_terms: D000465:Algorithms; D002450:Cell Communication; D005347:Fibroblasts / Q000166:cytology; D021621:Imaging, Three-Dimensional; D040542:Mechanotransduction, Cellular; D008853:Microscopy / Q000379:methods*; D009504:Neutrophils / Q000166:cytology; D012583:Schwann Cells / Q000166:cytology
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