Title page for ETD etd-3726103049751491


Type of Document Dissertation
Author Balderson, Stephanie D.
Author's Email Address baldersn@patriot.net
URN etd-3726103049751491
Title Investigations of Insulin-Like Growth Factor I Cell Surface Binding: Regulation by Insulin-Like Growth Factor Binding Protein-3 and Heparan Sulfate Proteoglycan
Degree Master of Science
Department Chemical Engineering
Advisory Committee
Advisor Name Title
Forsten-Williams, Kimberly Committee Chair
Misra, Hara P. Committee Member
Velander, William H. Committee Member
Keywords
  • Insulin-Like Frowth Factor Binding Protein-3
  • Insulin-Like Growth Factor
  • Mathematical Modeling
  • Heparan Sulfate Proteoglycan
Date of Defense 1997-05-22
Availability unrestricted
Abstract

The primary aim of this text is to gain insight on how

cellular activation by a insulin-like growth factor

(IGF-I), in the presence of insulin-like growth factor

binding protein-3 (IGFBP-3), is influenced by

heparan sulfate proteoglycans (HSPG). Initial

research will be presented, assumptions and

hypotheses that were included in the development of

mathematical models will be discussed, and the

future enhancements of the models will be explored.

There are many potential scenarios for how each

component might influence the others. Mathematical

modeling techniques will highlight the contributions

made by numerous extracellular parameters on

IGF-I cell surface binding. Tentative assumptions

can be applied to modeling techniques and

predictions may aid in the direction of future

experiments. Experimentally, it was found that

IGFBP-3 inhibited IGF-I Bovine Aortic Endothelial

(BAE) cell surface binding while p9 HS slightly

increased IGF-I BAE cell surface binding. IGFBP-3

has a higher binding affinity for IGF-I (3 x 10-9 M)

than p9 HS has for IGF-I (1.5 x 10-8 M) as

determined with cell-free binding assays. The

presence of p9 HS countered the inhibiting effect of

IGFBP-3 on IGF-I BAE cell surface binding.

Although preliminary experiments with labeled p9

HS and IGFBP-3 indicated little to no cell surface

binding, later experiments indicated that both

IGFBP-3 and p9 HS do bind to the BAE cell

surface. Pre-incubation of BAE cells with either

IGFBP-3 or p9 HS resulted in an increase of IGF-I

BAE cell surface binding . There was a more

substantial increase of IGF-I surface binding when

cells were pre-incubated with IGFBP-3 than p9

HS. There was a larger increase of IGF-I BAE cell

surface binding when cells were pre-incubated with

p9 HS than when p9 HS and IGF-I were added

simultaneously. This suggests that IGFBP-3 and p9

HS surface binding plays key role in IGF-I surface

binding, however, p9 HS surface binding does not

alter IGF-I surface binding as much as IGFBP-3

surface binding seems to. Experimental work helps

further the understanding of IGF-I cellular activation

as regulated by IGFBP-3 and p9 HS. Developing

mathematical models allows the researcher to focus

on individual elements in a complex systems and

gain insight on how the real system will respond to

individual changes. Discrepancies between the

model results and the experimental data presented

indicate that soluble receptor inhibition is not

sufficient to account for experimental results. The

alliance of engineering analysis and molecular

biology helps to clarify significant principles relevant

to the conveyance of growth factors into tissue.

Awareness of the effects of individual parameters in

the delivery system, made possible with

mathematical models, will provide guidance and

save time in the design of future therapeutics

involving growth factors.

Files
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  !ch2.pdf 86.26 Kb 00:00:23 00:00:12 00:00:10 00:00:05 < 00:00:01
  !ch3.pdf 93.41 Kb 00:00:25 00:00:13 00:00:11 00:00:05 < 00:00:01
  App.pdf 60.20 Kb 00:00:16 00:00:08 00:00:07 00:00:03 < 00:00:01
  Ch1.pdf 319.52 Kb 00:01:28 00:00:45 00:00:39 00:00:19 00:00:01
  Ch4.pdf 48.96 Kb 00:00:13 00:00:06 00:00:06 00:00:03 < 00:00:01
  Ch5.pdf 370.28 Kb 00:01:42 00:00:52 00:00:46 00:00:23 00:00:01
  Ch6.pdf 15.04 Kb 00:00:04 00:00:02 00:00:01 < 00:00:01 < 00:00:01
  Title.pdf 9.06 Kb 00:00:02 00:00:01 00:00:01 < 00:00:01 < 00:00:01
  Toc.pdf 13.71 Kb 00:00:03 00:00:01 00:00:01 < 00:00:01 < 00:00:01

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