Thermodynamic Insights into Protein Adsorption on Supramolecular Assemblies of π-Amphiphiles

Abstract

Nonspecific adsorption of proteins on the surface of nanocarriers plays a critical role in their cellular uptake and other biological functions. This article reports vesicular assemblies of two πamphiphiles (NDI-1 and NDI-2) and thermodynamic aspects of their interaction with bovine serum albumin (BSA). Both contain a hydrophobic naphthalene-diimide (NDI) core and two oligo-oxyethylene (OE) wedges but differ by the presence of the hydrazide group in NDI-1. NDI-2 exhibits a constricted π-stacking and enthalpy-driven adsorption of BSA. In contrast, NDI-1 exhibits a stronger interaction due to enhanced entropy contribution. It is postulated that a tight packing of NDI chromophores in NDI-2 results in an inadequate space in the corona, leading to the dehydration of OE chains, which contributes to the observed enthalpy-driven binding. On the other hand, due to H-bonding along the direction of π-stacking in NDI-1, an enhanced interchromophoric distance provides more space in the shell, resulting in less dehydration of the OE chains, which results in an entropy gain from the BSA binding-induced release of water from the OE chains. Intercalation of an electron-rich pyrene in the electron-deficient NDI-1 stack further reduces the grafting density of the OE chains, resulting in negligible BSA adsorption, similar to a stealth polymer. A correlation can be seen between the thermodynamic landscape of the protein adsorption and the trend of their lower critical solution temperature (LCST), which follows the order NDI-1 + Py < NDI-1 < NDI-2.

Amphiphilic Alternating Copolymers with an Adjustable Lower Critical Solution Temperature (LCST) and Correlation with Nonspecific Protein Adsorption

“…Understanding the fundamental aspects of such interactions is of close relevance to biological applications of any new nanocarriers in general because when administered in a physiological system, such issues greatly impact their cellular uptake and other biological functions. − While PEG-decorated systems have been extensively studied in this context, a newly introduced system, such as PU-6b with much shorter OEG chains exhibited at the surface, are less known Figure shows the ITC plot of the interaction of BSA with PU-6b at 22 °C (just around cloud point).…”

“…Inspired by these results, we further examined nonspecific adsorption of a model serum protein BSA on the OEG-occupied surface of the PU-6b capsule. First, it was probed by DLS study (Figure S15), which showed an increase in the D h of PU-6b from 300 to 470 nm in the presence of BSA, indicating the adsorption of the protein on the surface of the aggregates . We further examined the detailed thermodynamic aspects of such nonspecific protein adsorption by ITC studies (Figures and S16) and correlated the results with the LCST.…”

“…Δ H and Δ S are the molar enthalpy and entropy of BSA binding (ligand) to the macromolecule (here polymeric capsule), respectively, and K a is the binding constant. The details for the determination of thermodynamic parameters utilizing the “single set of binding sites” is discussed elsewhere …”

“…The details for the determination of thermodynamic parameters utilizing the "single set of binding sites" is discussed elsewhere. 41 ■ RESULTS AND DISCUSSION Synthesis and Characterization. Structures of the amphiphilic polyurethanes (PUs) are shown in Scheme 1.…”

“…58−62 While PEGdecorated systems have been extensively studied in this context, 63 a newly introduced system, such as PU-6b with much shorter OEG chains exhibited at the surface, are less known. 41 Figure 4 shows the ITC plot of the interaction of BSA with PU-6b at 22 °C (just around cloud point). From the obtained data, the nature of the interaction was found to be exothermic, which means the heat is released at every step of BSA being injected into the solution of the polymeric capsule.…”