title: Flow-Induced Crystallization of Collagen: A Potentially Critical Mechanism in Early Tissue Formation.
abstract: The type I collagen monomer is one of nature's most exquisite and prevalent structural tools. Its 300 nm triple-helical motifs assemble into tough extracellular fibers that transition seamlessly across tissue boundaries and exceed cell dimensions by up to 4 orders of magnitude. In spite of extensive investigation, no existing model satisfactorily explains how such continuous structures are generated and grown precisely where they are needed (aligned in the path of force) by discrete, microscale cells using materials with nanoscale dimensions. We present a simple fiber drawing experiment, which demonstrates that slightly concentrated type I collagen monomers can be "flow-crystallized" to form highly oriented, continuous, hierarchical fibers at cell-achievable strain rates (<1 s(-1)) and physiologically relevant concentrations (∼50 μM). We also show that application of tension following the drawing process maintains the structural integrity of the fibers. While mechanical tension has been shown to be a critical factor driving collagen fibril formation during tissue morphogenesis in developing animals, the precise role of force in the process of building tissue is not well understood. Our data directly couple mechanical tension, specifically the extensional strain rate, to collagen fibril assembly. We further derive a "growth equation" which predicts that application of extensional strains, either globally by developing muscles or locally by fibroblasts, can rapidly drive the fusion of already formed short fibrils to produce long-range, continuous fibers. The results provide a pathway to scalable connective tissue manufacturing and support a mechano-biological model of collagen fibril deposition and growth in vivo.
authors.affiliation: Department of Bioengineering, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Paten
authors.affiliation: Department of Bioengineering, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Siadat
authors.affiliation: Department of Bioengineering, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Susilo
authors.affiliation: Department of Bioengineering, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Ebraheim N
authors.initials: EN
authors.lastname: Ismail
authors.affiliation: Department of Bioengineering, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Jayson L
authors.initials: JL
authors.lastname: Stoner
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst , 160 Governors Drive, Amherst, Massachusetts 01003, United States.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Rothstein
authors.affiliation: Department of Bioengineering, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Ruberti
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry*; D024042:Collagen Type I / Q000737:chemistry*; D003460:Crystallization; D005109:Extracellular Matrix; D013314:Stress, Mechanical; D023822:Tissue Engineering
chemical_list: D024042:Collagen Type I; D003094:Collagen
keywords: collagen; development; extensional strain; flow-induced crystallization; self-assembly