Investigating the molecular origins of biocompatibility : intermolecular interactions between human serum albumin and various chemically modified surfaces via high resolution force spectroscopy

The first step in two of the most troublesome biological responses to the implantation of blood-contacting biomaterials, i.e. thrombosis and inflammation, is the adhesion of blood plasma proteins to the biomaterial surface, which may then initiate platelet adhesion and activation, and thereby set in motion a cascade of adverse host responses. If devices could be developed that prevent that first step from occurring altogether, a new generation of "stealth" biomaterials would be born. Such was the motivation of this project, which sought to investigate the constituent intermolecular interaction forces governing protein adhesion to biomaterials, using the technique of high resolution force spectroscopy. The model protein chosen for our study was human serum albumin (HSA), the smallest and most abundant blood protein in the human body, and typically the first to adsorb to a blood-contacting, implanted device. In the first stage of our investigation, HSA was covalently grafted to a nanosized probe tip at the end of a soft, microfabricated cantilever force transducer. The intermolecular interaction potential, U(D), was recorded between the HSA-modified probe tip and four different model surfaces, including: 1) gold, 2) a hydrophobic, CH3-terminated alkanethiol self-assembling monolayer (SAM), 3) a hydrophilic, COO-terminated alkanethiol SAM, and 4) individual, covalently end-grafted molecules of poly(ethylene oxide), in aqueous sodium phosphate buffer solution (PBS, ionic strength IS = 0.01M, pH = 7.4). Both theoretical and numerical modeling were employed to evaluate the experimental results on each of the different surfaces, and to characterize the nature of the protein-bound probe tip. In the second part of this study,

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Materials Science and Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Rixman, Monica Anne, 1977-

Advisor dc:contributor.advisor

• Christine Ortiz.

• Materials Science and Engineering.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/30118

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/30118