title: Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs.
abstract: In native states, animal cells of many types are supported by a fibrous network that forms the main structural component of the ECM. Mechanical interactions between cells and the 3D ECM critically regulate cell function, including growth and migration. However, the physical mechanism that governs the cell interaction with fibrous 3D ECM is still not known. In this article, we present single-cell traction force measurements using breast tumor cells embedded within 3D collagen matrices. We recreate the breast tumor mechanical environment by controlling the microstructure and density of type I collagen matrices. Our results reveal a positive mechanical feedback loop: cells pulling on collagen locally align and stiffen the matrix, and stiffer matrices, in return, promote greater cell force generation and a stiffer cell body. Furthermore, cell force transmission distance increases with the degree of strain-induced fiber alignment and stiffening of the collagen matrices. These findings highlight the importance of the nonlinear elasticity of fibrous matrices in regulating cell-ECM interactions within a 3D context, and the cell force regulation principle that we uncover may contribute to the rapid mechanical tissue stiffening occurring in many diseases, including cancer and fibrosis.
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Hall
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Farid
authors.initials: F
authors.lastname: Alisafaei
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Ban
authors.affiliation: Field of Theoretical and Applied Mechanics, Department of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853.
authors.forename: Xinzeng
authors.initials: X
authors.lastname: Feng
authors.affiliation: Field of Theoretical and Applied Mechanics, Department of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853.
authors.forename: Chung-Yuen
authors.initials: CY
authors.lastname: Hui
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104; mw272@cornell.edu vshenoy@seas.upenn.edu.
authors.forename: Vivek B
authors.initials: VB
authors.lastname: Shenoy
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853; mw272@cornell.edu vshenoy@seas.upenn.edu.
authors.forename: Mingming
authors.initials: M
authors.lastname: Wu
mesh_terms: D001696:Biomechanical Phenomena; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004548:Elasticity; D005109:Extracellular Matrix / Q000473:pathology*; D006801:Humans; D008465:Mechanoreceptors / Q000502:physiology; D018613:Microscopy, Confocal; D040081:Protein Array Analysis / Q000379:methods
chemical_list: D003094:Collagen
keywords: 3D cell traction force microscopy; cell traction force; cell–ECM interaction; collagen; fibrous nonlinear elasticity