(C-87) Unique Dipole Relaxation at Poly(propylene sulfone) Nanoparticle Interfaces Preserves Protein Functions

Introduction:: Protein adsorption onto surfaces is a crucial phenomenon that has been studied for decades for its promising application in biomaterials science and drug delivery. During the adsorption process, proteins unfold and denature in a thermodynamically-driven process to minimize energy at the biomaterial interface, often resulting in the loss of the proteins’ normal functions and eliciting undesirable cell interactions and inflammation. It is therefore highly advantageous to preserve protein structure and function when binding strongly to biomaterial and nanomaterial surfaces. Tuning the material surface chemistry such that the denaturation of proteins can be prevented remains an unsolved challenge. Poly(propylene sulfone) (referred to as PPSU) is a novel self-assembling homopolymer with strong dipoles that uniquely binds strongly with proteins without disrupting their structure or function (Fig 1A) (1,2). Here, via molecular modeling, we demonstrate that PPSU nanoparticles possess active surfaces that adjust their hydrophobicity upon contact with proteins by relaxing dipoles (Fig 1B, C). Therefore, PPSU is a promising material for a wide range of biomaterial applications.


Materials and Methods:: All-atom molecular dynamics (MD) was utilized to model PPSU polymers and their interactions with proteins (Trypsins, BSA, and GFP). GROMACS 2021 and CHARMM 36 forcefield were used to perform the simulations. The CGenff server was used to generate forcefield parameters for the PPSU molecule. The system was relaxed with energy minimization and equilibration. Subsequently, a long production run was performed. Structure and energy analyses were performed on each protein-PPSU complex to validate the irreversible and non-destructive binding and further reveal the binding mechanism.


Results, Conclusions, and Discussions:: A unique dipole relaxation was found to be responsible for the strong yet non-denaturing surface binding. The sulfone groups generate strong dipoles in the PPSU chains. Upon contact with proteins, the sulfone groups rotate around the chains such that the dipole orientation of the polymer aligns with the protein surface dipoles, significantly enhancing the protein binding (Fig 1B, C). Furthermore, dipole-dipole interactions are short-range reactions that quickly fade with distance to the third power. Therefore, the dipole-dipole interactions only affect the protein surfaces, without disrupting the core structures of the proteins. In conclusion, the dipole enrichment and relaxation provide PPSU with the ability to irreversibly capture proteins without denaturation. Based on the unique properties of PPSU nanoparticles, various biomedical applications can be developed such as multi-drug co-delivery, surface display of bioactive enzymes, and complex multi-antibody coatings with facile stoichiometric control.


Acknowledgements (Optional): :

References (Optional): : (1) Du et al., Homopolymer self-assembly of poly(propylene sulfone) hydrogels via dynamic noncovalent sulfone-sulfone bonding. Nat. Commun. 2020. DOI: 10.1038/s41467-020-18657-5

(2) Du, Rische, & Li et al., Bioactive multi-protein adsorption enables targeted mast cell nanotherapy. Nat. Nanotechnol. Under Review. DOI: 10.21203/rs.3.rs-2468299/v1.