AVS 46th International Symposium
    Biomaterial Interfaces Group Wednesday Sessions
       Session BI-WeP

Paper BI-WeP14
Design of a Minimal Peptide for Adsorption to Hydroxyapatite and Cell Binding via an RGD Sequence

Wednesday, October 27, 1999, 5:30 pm, Room 4C

Session: Poster Session
Presenter: M. Gilbert, University of Washington
Authors: M. Gilbert, University of Washington
C.M. Giachelli, University of Washington
P.S. Stayton, University of Washington
Correspondent: Click to Email
In the natural remodeling of bone, the proteins that comprise the extracellular matrix play keys roles in the signaling of bone cells. These ECM proteins contain amino acid sequences such as RGD which are important for the adhesion of bone cells to the protein coated bone surface as well as the transmission of signals via outside-in integrin pathways. Many of the ECM proteins also contain stretches of acidic amino acid repeats, gamma carboxyglutamic acid residues, or high degrees of sulfation, glycosolation, or phosphorylation which aid in the adsorption of the protein to the mineral surface of bone. Despite the large body of knowledge on bone biology, most modern bone implant designs do not employ any control over the degree or specificity of protein adsorption to the surface of the implant which can result in lack of integration of the implant or encapsulation of the implant. However, by understanding how the biomineralization proteins bind to mineral surfaces and transmit signals to bone cells, minimal peptides can be designed which contain the features of strong mineral adsorption as well as integrin mediated cell adhesion and intracellular signaling to improve implant integration. A minimal peptide based on the mineral binding motif of salivary statherin combined with an RGD sequence was designed to bind and orient on hydroxyapatite surfaces. This fusion peptide (called N15-RGD) is capable of binding with high affinity to hydroxyapatite with the same Langmuir parameters as just N15 as well as maintaining alpha helical content in solution. N15-RGD, while immobilized on HAP, is also capable of binding cells specifically and in a dose dependent manner via the RGD sequence. The main integrin responsible for the binding of the cells to the RGD sequence is the @alpha@@sub v@@beta@@sub 3@ integrin. The N15-RGD peptide is thus oriented in such a manner that the RGD cell signaling sequence is still solution accessible to mediate integrin binding events.