Spatial control of ligand presentation on biomaterial surfaces
Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1999.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2010
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/57669 |
| _version_ | 1826192862647156736 |
|---|---|
| author | Brown, Gillian Louise |
| author2 | Linda G. Griffith. |
| author_facet | Linda G. Griffith. Brown, Gillian Louise |
| author_sort | Brown, Gillian Louise |
| collection | MIT |
| description | Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1999. |
| first_indexed | 2024-09-23T09:30:20Z |
| format | Thesis |
| id | mit-1721.1/57669 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T09:30:20Z |
| publishDate | 2010 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/576692019-04-10T12:41:41Z Spatial control of ligand presentation on biomaterial surfaces Brown, Gillian Louise Linda G. Griffith. Massachusetts Institute of Technology. Dept. of Materials Science and Engineering. Massachusetts Institute of Technology. Dept. of Materials Science and Engineering. Materials Science and Engineering. Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1999. Includes bibliographical references (leaves 201-211). Adhesion of many cell types to the extracellular matrix or to synthetic bioactive surfaces is mediated by transmembrane integrin receptors. Integrin clustering is believed to be closely associated with focal contact formation and signaling, as assessed by the behavior of cells on surfaces presenting relatively uniform ligand distributions. It has therefore been hypothesized that controlled clustering of 2, 3.....n integrins might be achieved by controlling the spatial distribution of adhesion ligands on biomaterial surfaces. Substrates were prepared on which cell-surface interactions are controlled by modifying non-adhesive poly(ethylene oxide) (PEO) hydrogels with the minimal cell-adhesion peptide sequence GRGDY (RGD). The peptide is tethered to the hydrogel surfaces via star PEO molecules, producing surfaces on which the ligands are presented to cells in "clusters", or domains of high concentration. The substrates are compared with others on which the RGD peptide is uniformly distributed. Control of the RGD cluster size was achieved by varying the relative concentrations of reactants in solution. The binding of RGD-modified stars to surfaces was found to be a non-linear function of its concentration in solution and degree of modification, and is reasonably explained by a Langmuir model of competitive adsorption. Quantitative techniques for visualizing the ligand distribution on the surface were developed, and indicated that surfaces to which ligands had been tethered via star molecules showed a significant deviation from normal, random distribution. Thus, control of the ligand spatial distribution was achieved. In addition, preliminary biological testing suggests that substrates on which adhesion ligands are presented to cells in a clustered format produces more physiological behaviour than those on which ligands are uniformly distributed at the same average ligand density. Thus, we have fabricated surfaces which, because of their resistance to non-specific cell interactions and the control of specific interactions at the molecular level, can serve as a model for artificial matrix development and can be used for fundamental in vitro studies. by Gillian L. Brown. Ph.D. 2010-08-30T14:26:34Z 2010-08-30T14:26:34Z 1999 1999 Thesis http://hdl.handle.net/1721.1/57669 45232684 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 220 leaves application/pdf Massachusetts Institute of Technology |
| spellingShingle | Materials Science and Engineering. Brown, Gillian Louise Spatial control of ligand presentation on biomaterial surfaces |
| title | Spatial control of ligand presentation on biomaterial surfaces |
| title_full | Spatial control of ligand presentation on biomaterial surfaces |
| title_fullStr | Spatial control of ligand presentation on biomaterial surfaces |
| title_full_unstemmed | Spatial control of ligand presentation on biomaterial surfaces |
| title_short | Spatial control of ligand presentation on biomaterial surfaces |
| title_sort | spatial control of ligand presentation on biomaterial surfaces |
| topic | Materials Science and Engineering. |
| url | http://hdl.handle.net/1721.1/57669 |
| work_keys_str_mv | AT browngillianlouise spatialcontrolofligandpresentationonbiomaterialsurfaces |