Effects of Ionic Strength on the Morphology, Scattering, and Mechanical Response of Neurofilament-Derived Protein Brushes

Abstract

Protein brushes not only play a key role in the functionality of neurofilaments but also have wide applications in biomedical materials. Here, we investigate the effect of ionic strength on the morphology of protein brushes using continuousspace self-consistent field theory. A coarse-grained multiblock charged macromolecular model is developed to capture the chemical identity of amino acid sequences. For neurofilament heavy (NFH) brushes at pH 2.4, we predict three morphological regimes: swollen brushes, condensed brushes, and coexisting brushes, which consist of both a dense inner layer and a diffuse outer layer. The brush height predicted by our theory is in good agreement with the experimental data for a wide range of ionic strengths. The dramatic height decrease is a result of the electrostatic screening-induced transition from the overlapping state to the isolated state of the coexisting brushes. We also studied the evolution of the scattering and mechanical responses accompanying the morphological change. The oscillation in the reflectivity spectra characterizes the existence and microstructure of the inner condensed layer, whereas the shoulder in the force spectra signifies a swollen morphology.

Dissecting neurofilament tail sequence-phosphorylation-structure relationships with multicomponent reconstituted protein brushes

“…At low ionic strengths the model underpredicts brush height, which is attributed to the simplified treatment of a uniform dielectric environment with the dielectric constant of water. The lower dielectric constant of proteins in real brushes would amplify charge repulsion to increase brush height, and the dielectric contrast between the brush and the substrate would also increase brush height via image charge repulsion 31 . At intermediate ionic strengths, the SCFT overestimates the height of phosphorylated NFH brushes, which can be attributed to the lack of explicit treatment of proton dissociation 44 .…”

“…Each protein is treated as a Gaussian chain with N number of segments of volume v and Kuhn length b . After following the standard procedures ( 31 , refs. 48—52) to decouple the interacting system, and using the saddle point approximation, we obtain a series of continuous-space, self-consistent field equations.…”

“…An SCFT was applied as described previously 31 . A detailed derivation is presented in Supporting Note 1 and details on charge density and Flory-Huggins parameters are presented in Supporting Note 2.…”

“…SCFT is well-suited to modeling inhomogeneous polymer systems, providing polymer density profiles that are experimentally inaccessible. We applied a continuous-space SCFT previously developed for NF tail brushes 31 , which systematically includes the elastic energy due to protein chain deformation, short-range residue hydrophobicity via the Flory-Huggins parameter, and electrostatic interactions. We employed a coarse-graining procedure in which each amino acid sequence is mapped onto a multi-block copolymer model, where each block is parameterized by the average hydrophobicity and charge of its constituent residues at the chosen pH.…”

Neurofilament Biophysics: From Structure to Biomechanics

“…Self-consistent field theory (SCFT) is also well suited to studying polymer brushes and has also been applied to the NF tails ( Zhulina and Leermakers, 2009 ; Yokokura et al. , 2023 ).…”