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bioRxiv · 10.1101/2025.09.07.674647

Effects of arginine on the interfacial behavior of proteins

Dastyar, P.·Mitra, H.·Wood, C. V.·Lin, Y.-J.·Tian, Y.·Ardekani, A.
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Abstract

HypothesisProtein adsorption at fluid-fluid interfaces can induce conformational rearrangements and promote aggregation. Arginine, as an amino acid is known to attenuate protein-protein interactions and lower the viscosity of protein formulations. Given its surface-active properties, we hypothesize that arginine may be effective in limiting aggregation at fluid-fluid interfaces. ExperimentsInterfacial rheology of Etanercept (Enbrel), Immunoglobulin G1 (IgG1), and Bovine Serum Albumin (BSA) was characterized across a range of concentrations, with and without L-arginine Hydrochloride. The interfacial response was examined in both linear and nonlinear regimes.{zeta} -potential was also measured for selected formulations to evaluate the relationship between electrostatic characteristics and the rheological outcomes. FindingsBased on both linear and nonlinear interfacial rheology results, arginine generally weakened protein-protein interactions; however, the effect depends on protein identity and concentration. In arginine-containing formulations, Enbrel and BSA displayed only minor variation in interfacial viscoelasticity between 0.01 and 1 mg/mL, particularly during prolonged aging; in contrast, IgG1 showed larger concentration-dependent differences. These results strengthen predictive frameworks for interfacial stability and guide the rational design of protein-amino acid biopharmaceutical formulations. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/674647v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@10a0bc8org.highwire.dtl.DTLVardef@8b9be7org.highwire.dtl.DTLVardef@1a88e43org.highwire.dtl.DTLVardef@113d5a9_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Dastyar, P., Mitra, H., Wood, C. V., Lin, Y.-J., Tian, Y., Ardekani, A.. 2025-09-12. Effects of arginine on the interfacial behavior of proteins. https://doi.org/10.1101/2025.09.07.674647

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