title: Self healing hydrogels composed of amyloid nano fibrils for cell culture and stem cell differentiation.
abstract: Amyloids are highly ordered protein/peptide aggregates associated with human diseases as well as various native biological functions. Given the diverse range of physiochemical properties of amyloids, we hypothesized that higher order amyloid self-assembly could be used for fabricating novel hydrogels for biomaterial applications. For proof of concept, we designed a series of peptides based on the high aggregation prone C-terminus of Aβ42, which is associated with Alzheimer's disease. These Fmoc protected peptides self assemble to β sheet rich nanofibrils, forming hydrogels that are thermoreversible, non-toxic and thixotropic. Mechanistic studies indicate that while hydrophobic, π-π interactions and hydrogen bonding drive amyloid network formation to form supramolecular gel structure, the exposed hydrophobic surface of amyloid fibrils may render thixotropicity to these gels. We have demonstrated the utility of these hydrogels in supporting cell attachment and spreading across a diverse range of cell types. Finally, by tuning the stiffness of these gels through modulation of peptide concentration and salt concentration these hydrogels could be used as scaffolds that can drive differentiation of mesenchymal stem cells. Taken together, our results indicate that small size, ease of custom synthesis, thixotropic nature makes these amyloid-based hydrogels ideally suited for biomaterial/nanotechnology applications.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Reeba S
authors.initials: RS
authors.lastname: Jacob
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Santanu K
authors.initials: SK
authors.lastname: Basu
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Narendra Nath
authors.initials: NN
authors.lastname: Jha
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India; IITB Monash Research Academy, IIT Bombay, Powai, Mumbai 400076, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Das
authors.affiliation: Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Sukul
authors.affiliation: Institute of Chemical Technology, Matunga, Mumbai, Maharashtra 400031, India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Patil
authors.affiliation: Institute of Chemical Technology, Matunga, Mumbai, Maharashtra 400031, India.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Sathaye
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Arindam
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
authors.forename: Sudip
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
authors.forename: Shamik
authors.initials: S
authors.lastname: Sen
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India. Electronic address: samirmaji@iitb.ac.in.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000682:Amyloid; D020100:Hydrogels
keywords: Amyloid hydrogel; Nanofibrils; Self-assembly; Stem cell; Tissue engineering