Abstract
Hierarchical assemblies of proteins into fibrillar structures occur in both physiologic and pathologic extracellular spaces and often involve interactions between oppositely charged peptide domains. However, the interplay between tertiary structure dynamics and quaternary hierarchical structure formation remains unclear. In this work, we investigate supramolecular mimics of these systems by mixing one-dimensional assemblies of small alkylated peptides bearing opposite charge and varying in peptide sequence. We found that assemblies with weak cohesive interactions readily create fibrous superstructures of bundled filaments as molecules redistribute upon mixing. Low cohesion allows molecules to escape from the original assemblies and exchange dynamics help them reassemble into electrostatically stable bundles. However, we also found that kinetic barriers can be encountered in these systems and limit formation of the hierarchical structures at pH values where charge densities are high. Increasing intermolecular cohesion using longer peptide sequences that form stable β-sheets was found to suppress superstructure formation. Our findings suggest that low internal cohesion in protein systems could facilitate the conformational rearrangements required to create hierarchical structures.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12216-12225 |
| Number of pages | 10 |
| Journal | Journal of the American Chemical Society |
| Volume | 142 |
| Issue number | 28 |
| DOIs | |
| State | Published - Jul 15 2020 |
Funding
This work was primarily funded by Center for Bio-Inspired Energy Science (CBES), an Energy Frontier Research Center (EFRC) funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DE-SC0000989 (for X-ray scattering experiments and cryogenic TEM experiments). Additional support for conventional TEM and SEM studies was provided through a gift from the Shannon Family Fund for Bio-Inspired and Bioactive Materials Systems for Musculoskeletal Regeneration. J.R.W. acknowledges financial support from the Weinberg Undergraduate Research Grant Program of Northwestern University’s Weinberg College of Arts and Sciences. J.A.L. acknowledges financial support by an NSF Graduate Research Fellowship (Grant DGE-1324585). The authors are grateful to Mark Karver of the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University for his expertise and assistance in peptide amphiphile synthesis and purification; Mark Seniw for the preparation of graphical illustrations shown throughout this manuscript; Ivan Sasselli for assistance with FTIR experimentation as well as for helpful discussions; Mark McClendon for providing assistance with SEM experiments; and Nicholas Sather for providing supplemental TEM micrographs. This work utilized the Peptide Synthesis Core Facility (peptide synthesis) and the Analytical BioNanoTechnology Core (chemical and biological analysis), both at the Simpson Querrey Institute at Northwestern University. The Simpson Querrey Institute, Northwestern University Office for Research, U.S. Army Research Office, and the U.S. Army Medical Research and Materiel Command have provided funding to develop both of these facilities and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS – 1542205). This work made use of the EPIC facility of the Northwestern NUANCE center, which has received support from SHyNE Resource (NSF ECCS – 1542205); the MRSEC program (NSF DMR – 1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Imaging work was also performed at the Biological Imaging Facility (BIF) and the Center for Advanced Microscopy (CAM) at Northwestern University. BIF is supported by the Chemistry for Life Processes Institute, the NU Office for Research, and the Rice Foundation, and CAM is supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Solution X-ray experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. Use of APS, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357.
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry