Annals of Biomedical Engineering

, 34:618

Regulation of Insulin-Like Growth Factor-I (IGF-I) Delivery by IGF Binding Proteins and Receptors

Authors

  • Julie M. D. Paye
    • Department of Chemical EngineeringVirginia Polytechnic Institute and State University
    • Department of Chemical EngineeringVirginia Polytechnic Institute and State University
    • Department of Chemical EngineeringVirginia Polytechnic Institute and State University
Article

DOI: 10.1007/s10439-005-9064-6

Cite this article as:
Paye, J.M.D. & Forsten-Williams, K. Ann Biomed Eng (2006) 34: 618. doi:10.1007/s10439-005-9064-6

Abstract

Delivery of growth factors via the bloodstream for the treatment of various diseases is regulated in part by interactions with cell surface binding elements. Understanding the kinetics of growth factor binding and transport by cells would, therefore, be advantageous. This report quantifies the binding, internalization, and transport of insulin-like growth factor-I (IGF-I) across bovine aortic endothelial cells (BAEC) cultured in vitro. Binding analysis indicated that IGF binding proteins (IGFBPs), primarily localized with the extracellular matrix, were the primary IGF-I binding elements in our system, with twice as many binding sites (8.0 ± 1.9 × 104 per cell) as IGF-I receptors (IGF-IR) (3.9 ± 0.6 × 104 per cell). Internalization of IGF-I by IGF-IR, but not IGFBPs, was detected, however both receptor and IGFBP binding were shown to inhibit rather than enhance the transport of intact IGF-I, albeit in different ways. IGFBPs retained IGF-I in the apical region while IGF-IR binding led to protein degradation. Based on our computational modeling and experimental data, we hypothesize that IGFBPs could function as a reservoir for IGF-I, sequestering it for later release and transport, and that this reservoir function of the IGFBPs could be used to promote controlled localized delivery of IGF-I.

Keywords

TranscytosisInsulin-like growth factor receptor (IGFIR)Insulin-like growth factor binding proteinsEndocytosisMathematical modelingBovine aortic endothelial cells Trafficking

Copyright information

© Biomedical Engineering Society 2006