title: Long-range mechanical force enables self-assembly of epithelial tubular patterns.
abstract: Enabling long-range transport of molecules, tubules are critical for human body homeostasis. One fundamental question in tubule formation is how individual cells coordinate their positioning over long spatial scales, which can be as long as the sizes of tubular organs. Recent studies indicate that type I collagen (COL) is important in the development of epithelial tubules. Nevertheless, how cell-COL interactions contribute to the initiation or the maintenance of long-scale tubular patterns is unclear. Using a two-step process to quantitatively control cell-COL interaction, we show that epithelial cells developed various patterns in response to fine-tuned percentages of COL in ECM. In contrast with conventional thoughts, these patterns were initiated and maintained by traction forces created by cells but not diffusive factors secreted by cells. In particular, COL-dependent transmission of force in the ECM led to long-scale (up to 600 μm) interactions between cells. A mechanical feedback effect was encountered when cells used forces to modify cell positioning and COL distribution and orientations. Such feedback led to a bistability in the formation of linear, tubule-like patterns. Using micro-patterning technique, we further show that the stability of tubule-like patterns depended on the lengths of tubules. Our results suggest a mechanical mechanism that cells can use to initiate and maintain long-scale tubular patterns.
authors.affiliation: Bioengineering, California Institute of Technology, MS 138-78, 1200 East California Boulevard, Pasadena, CA 91125, USA. guochin@caltech.edu
authors.forename: Chin-Lin
authors.initials: CL
authors.lastname: Guo
authors.forename: Mingxing
authors.initials: M
authors.lastname: Ouyang
authors.forename: Jiun-Yann
authors.initials: JY
authors.lastname: Yu
authors.forename: Jordan
authors.initials: J
authors.lastname: Maslov
authors.forename: Andrew
authors.initials: A
authors.lastname: Price
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Shen
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D004058:Diffusion / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020830:rac1 GTP-Binding Protein