title: Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.
abstract: Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression models were investigated to determine the relationships between composition/structure, dynamic processes, and mechanical properties. Mediation was then used to determine if dynamic processes mediated structure-function relationships. Dynamic processes were strong predictors of mechanical properties. These predictions were location-dependent, with the insertion site utilizing all four dynamic responses and the midsubstance responding primarily with fibril deformation and sliding. In addition, dynamic processes were moderately predicted by composition and structure in a regionally-dependent manner. Finally, dynamic processes were partial mediators of the relationship between composition/structure and mechanical function, and results suggested that mediation is likely shared between multiple dynamic processes. In conclusion, the mechanical properties at the midsubstance of the tendon are controlled primarily by fibril structure and this region responds to load via fibril deformation and sliding. Conversely, the mechanical function at the insertion site is controlled by many other important parameters and the region responds to load via all four dynamic mechanisms. Overall, this study presents a strong foundation on which to design future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon.
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104-6081, United States.
authors.forename: Brianne K
authors.initials: BK
authors.lastname: Connizzo
authors.affiliation: Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Adams
authors.affiliation: Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Adams
authors.affiliation: Division of Biostatistics, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Abbas F
authors.initials: AF
authors.lastname: Jawad
authors.affiliation: Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Birk
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104-6081, United States. Electronic address: soslowsk@upenn.edu.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000235:genetics / Q000502:physiology; D018345:Mice, Knockout; D008954:Models, Biological; D012044:Regression Analysis; D017006:Rotator Cuff / Q000033:anatomy & histology / Q000502:physiology; D013710:Tendons / Q000033:anatomy & histology* / Q000502:physiology*
chemical_list: D003094:Collagen
keywords: Hierarchical; Mechanics; Regression; Supraspinatus tendon