Collagen fibril surface displays a constellation of sites capable of promoting fibril assembly, stability, and hemostasis.
Fibrillar collagens form the structural basis of organs and tissues including the vasculature, bone, and tendon. They are also dynamic, organizational scaffolds that present binding and recognition sites for ligands, cells, and platelets. We interpret recently published X-ray diffraction findings and use atomic force microscopy data to illustrate the significance of new insights into the functional organization of the collagen fibril. These data indicate that collagen's most crucial functional domains localize primarily to the overlap region, comprising a constellation of sites we call the "master control region." Moreover, the collagen's most exposed aspect contains its most stable part-the C-terminal region that controls collagen assembly, cross-linking, and blood clotting. Hidden beneath the fibril surface exists a constellation of "cryptic" sequences poised to promote hemostasis and cell-collagen interactions in tissue injury and regeneration. These findings begin to address several important, and previously unresolved, questions: How functional domains are organized in the fibril, which domains are accessible, and which require proteolysis or structural trauma to become exposed? Here we speculate as to how collagen fibrillar organization impacts molecular processes relating to tissue growth, development, and repair.
Pritzker Institute of Biomedical Science and Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA. orgel@iit.edu
J P R O
JP
Orgel
O
O
Antipova
I
I
Sagi
A
A
Bitler
D
D
Qiu
R
R
Wang
Y
Y
Xu
J D
JD
San Antonio
D000818:Animals; D001665:Binding Sites; D024022:Fibrillar Collagens / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D006487:Hemostasis; D007798:Lampreys; D008024:Ligands; D018625:Microscopy, Atomic Force; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D051381:Rats; D013499:Surface Properties
D024022:Fibrillar Collagens; D008024:Ligands