The Effect of Polymer Chain Mobility on Protein Adsorption and Subsequent Cell Behavior
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Many cell types are known to respond to the stiffness of polymeric biomaterial substrates. However, the mechanism by which cells sense this stiffness is still under investigation. Cell response to a material is believed to be mediated by the composition and/or configuration of the protein layers that adsorb to the biomaterial surfaces prior to cell contact. It is, therefore, hypothesized that polymer stiffness, and specifically, the flexibility of the polymer chains at the polymer aqueous interface, affects the composition and configuration of the adsorbed protein layer, which is responsible for influencing cell response. In this thesis, two biomaterials known to induce stiffness dependent cell responses are used as model systems to determine whether polymer chain flexibility influences cell behavior via differences in the protein adsorption. The first is an elastomer formed from an acrylated star-poly(D,L-lactide-co-ϵ-caprolactone) (ELAS) which has been shown to support higher NIH3T3 fibroblast proliferation on a less stiff version of the elastomer despite minimal differences in surface chemistry. The second is poly(trimethylene carbonate) (PTMC) which has been shown to degrade in vivo via macrophage mediated erosion at molecular weights higher than 100 kg/mol, but does not degrade at molecular weights of less than 70 kg/mol, despite no difference in surface chemistry. Quantity and viscoelastic properties of protein layers adsorbed from individual solutions of albumin, immunoglobulin G, fibronectin and vitronectin, as well as fetal serum and adult plasma supplemented environments were compared on different stiffnesses of these materials to determine whether polymer chain flexibility affects protein adsorption. Polymer stiffness was found to affect quantity and conformation of individually adsorbed protein layers as well as the composition of protein layers adsorbed from serum and plasma supplemented media. Surface adsorbed fetuin A and vitronectin were identified and proposed to be responsible for influencing fibroblast proliferation and macrophage behavior, respectively. It was concluded that the flexibility of the polymer chains at the polymer-aqueous interface affects the arrangement of water molecules at the interface and alters the entropic gain associated with protein adsorption, thus favoring the adsorption of different types and adsorbed conformation of proteins which influences the subsequent cell response to the biomaterial.