title: Selective Detection of RGD-Integrin Binding in Cancer Cells Using Tip Enhanced Raman Scattering Microscopy.
abstract: Ligand-receptor interactions play important roles in many biological processes. Cyclic arginine-glycine-aspartic acid (RGD) containing peptides are known to mimic the binding domain of extracellular matrix protein fibronectin and selectively bind to a subset of integrin receptors. Here we report the tip enhanced Raman scattering (TERS) detection of RGD-functionalized nanoparticles bound to integrins produces a Raman scattering signal specific to the bound protein. These results demonstrate that this method can detect and differentiate between two different integrins (α5β1 and αvβ3) bound to RGD-conjugated gold nanoparticles both on surfaces and in a cancer cell membrane. In situ measurements of RGD nanoparticles bound to purified α5β1 and αvβ3 receptors attached to a glass surface provide reference spectra for a multivariate regression model. The TERS spectra observed from nanoparticles bound to cell membranes are analyzed using this regression model and the identity of the receptor can be determined. The ability to distinguish between receptors in the cell membrane provides a new tool to chemically characterize ligand-receptor recognition at molecular level and provide chemical perspective on the molecular recognition of membrane receptors.
authors.affiliation: Department of Chemistry & Biochemistry, University of Notre Dame , 251 Nieuwland Science Hall, Notre Dame, Indiana 46556, United States.
authors.forename: Lifu
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Chemistry & Biochemistry, University of Notre Dame , 251 Nieuwland Science Hall, Notre Dame, Indiana 46556, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Chemistry & Biochemistry, University of Notre Dame , 251 Nieuwland Science Hall, Notre Dame, Indiana 46556, United States.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Schultz
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006046:Gold / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry; D008853:Microscopy / Q000295:instrumentation*; D010456:Peptides, Cyclic / Q000032:analysis / Q000378:metabolism*; D011485:Protein Binding; D013059:Spectrum Analysis, Raman / Q000295:instrumentation*
chemical_list: D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D006046:Gold