3 years ago

Kinetic Model for Two-Step Nucleation of Peptide Assembly

Kinetic Model for Two-Step Nucleation of Peptide Assembly
Martha A. Grover, David G. Lynn, Ming-Chien Hsieh
Intermediate dynamic assemblies are increasingly seen as necessary for the initial desolvation and organization of biomaterials to achieve their final crystalline order. Here we present a general peptide assembly model for two-step nucleation. The model predicts the phase transitions and equilibria between different phases by employing a combination of the Flory–Huggins parameter, the particle growth constant, and the binding energy to assemblies. Monte Carlo simulations are used to demonstrate how the system evolves from pure solution phases to the final thermodynamic assembly phase via an intermediate metastable particle phase. The final state of the system is determined by the solubility of the particle and assembly phases, where the phase with the lower solubility accumulates. A rare three-phase equilibrium exists when the solubilities of the particles and assemblies are similar. Experimental support for this model is achieved with assembly of the amyloid peptide Ac-KLVFFAE-NH2 (Aβ(16–22)) in mixed acetonitrile/water systems. Increasing the acetonitrile concentration decreases the number of particles, increases the particle size, and accelerates the assembly rate, all consistent with acetonitrile increasing the Aβ(16–22) peptide’s solubility of particles but with little influence on the stability of the assemblies. Taken together, our model captures the transition from the metastable particle phase to the higher order peptide assembly through two-step nucleation.

Publisher URL: http://dx.doi.org/10.1021/acs.jpcb.7b03085

DOI: 10.1021/acs.jpcb.7b03085

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.