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Review Article Volume 13 Issue 3
Aggregation of hydrophobic proteins: size dependent behavior and crossover to instability
Neha VK, Himadri B Bohidar
Received: June 30, 2026 | Published: July 16, 2026
Citation: Neha VK, Bohidar HB. Aggregation of hydrophobic proteins: size dependent behavior and crossover to instability. J Appl Biotechnol Bioeng. 2026;13(3):91-98. DOI: 10.15406/jabb.2026.13.00422
Abstract
In this study, the aggregation properties of mainly hydrophobic proteins are explored by using an extended DLVO model that included an extra short-range interaction. Two different interaction regimes are studied to isolate the effect of hydrophobic interactions on protein aggregation. In the first interaction regime, van der Waals attraction, electrostatic doublelayer repulsion, and short-range surface interactions are considered, and the interaction curves are described by finite energy barriers that kinetically stabilize protein dispersions over a broad size (R = 5-100 nm) and hydrophobicity (h f = 0-20 %) range. In the second interaction regime, hydrophobic attraction is described by an exponential potential, causing the electrostatic barrier to collapse beyond a critical size, and resulting in a diffusionlimited, irreversible protein aggregation. The maximum interaction force (F max) - size scaling analysis shows, Fmax ~ R±α, with α = 0.5 for the first interaction regime, whereas in the second (hydrophobicity-dominated) interaction regime, this scaling linearly decreases with size (α = -0.5), indicating the lack of finite energy barriers and the dominance of shortrange attraction. These results demonstrate that hydrophobic interactions by themselves are capable of inducing aggregation in electrostatically balanced systems. As a test, aggregation pattern in two predominantly hydrophobic proteins, elastin and zein, are discussed within the framework of Model-2 with satisfactory outcomes. Overall, this study clearly shows a size-dependent crossover from attraction-dominated behavior at small sizes to an unstable interaction regime at larger sizes, a conclusion that can be extended to colloidal, intrinsically disordered proteins and nanoparticle systems where surface hydrophobicity is profound. Graphical abstract Interaction mechanisms in predominantly hydrophobic proteins lead to size dependent cross-over to instability due to increased hydrophobicity.
Keywords: hydrophobic protein aggregation, non-DLVO model, interaction potential, size-dependent crossover, interaction force-particle size scaling
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