title: Poly(carboxybetaine methacrylamide)-modified nanoparticles: a model system for studying the effect of chain chemistry on film properties, adsorbed protein conformation, and clot formation kinetics.
abstract: Nonfouling polymer architectures are considered important to the successful implementation of many biomaterials. It is thought that how these polymers induce conformational changes in proteins upon adsorption may dictate the fate of the device being utilized. Herein, oxidized silicon nanoparticles (SiNP) were modified with various forms of poly(carboxybetaine methacrylamide) (PCBMA) for the express purpose of understanding how polymer chemistry affects film hydration, adsorbed protein conformation, and clot formation kinetics. To this end, carboxybetaine monomers differing in intercharge separating spacer groups were synthesized, and nitroxide-mediated free radical polymerization (NMP) was conducted using alkoxyamine initiators with hydrophobic (TEMPO) and hydrophilic (β-phosphonate) terminal groups. The physical properties (surface composition, thickness, grafting density, etc.) of the resulting polymer-SiNP conjugates were quantified using several techniques, including Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and thermogravimetric analysis (TGA). The effect of spacer group on the surface charge density was determined using zeta potential measurements. Three proteins, viz., lysozyme, bovine α-lactalbumin, and human serum albumin, were used to evaluate the effect film properties (charge, hydration, end-group) have on adsorbed protein conformation, as determined by circular dichroism (CD), fluorescence spectroscopy, and fluorescence quenching techniques. Hemocompatibility of these surfaces was observed by measuring clot formation kinetics using the plasma recalcification time assay. It was found that chain chemistry, as opposed to end-group chemistry, was a major determiner for water structure, adsorbed protein conformation, and clotting kinetics. It is thought that the systematic evaluation of how both chain (internal) and end-group (external) polymer properties affect film hydration, protein conformation, and clot formation will provide valuable insight that can be applied to all engineered surfaces for biomedical applications.
authors: Chemical and Materials Engineering Department, University of Alberta, National Research Council Canada, National Institute for Nanotechnology, Edmonton, Alberta, Canada.
authors: Sinoj
authors: S
authors: Abraham
authors: Alan
authors: A
authors: So
authors: Larry D
authors: LD
authors: Unsworth
mesh_terms: D000178:Acrylamides / Q000737:chemistry* / Q000378:metabolism; D000327:Adsorption; D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002417:Cattle; D002942:Circular Dichroism; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D058105:Polymerization; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D012825:Silicon / Q000737:chemistry; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D000178:Acrylamides; D020099:Coated Materials, Biocompatible; D012709:Serum Albumin; D012996:Solutions; D001622:Betaine; D007768:Lactalbumin; D009113:Muramidase; C045985:methacrylamide; D012825:Silicon