Gelatin grafted poly(D,L-lactide) as an inhibitor of protein aggregation: An in vitro case study.

Abstract

Amyloids are a group of proteins that are capable of forming aggregated amyloid fibrils, which is responsible for many neurodegenerative diseases including Alzheimer's disease (AD). In our previous study, synthesis and characterization of star-shaped poly(D,L-lactide)-b-gelatin (ss-pLG) have been reported. In the present work, we have extended our work to study ss-pLG against protein aggregation. To the best of our knowledge, this is the first report on the inhibition of amyloid fibrillation by protein grafted poly(D,L-lactide). Bovine serum albumin (BSA) was chosen as the model protein, which readily forms fibril under high temperature. We found that ss-pLG efficiently suppressed the fibril formation of BSA compared with gelatin (Gel), which was supported by Thioflavin T assay, circular dichroism (CD) spectroscopy and atomic force microscopy (AFM). In addition, ss-pLG significantly curtailed amyloid-induced hemolysis. We also found that incubation of ss-pLG with neuroblastoma cells (MC65) protected the cells from fibril-induced toxicity. The rescuing efficiency of ss-pLG was better than Gel, which could be attributed to the reduced lamella thickness in branched ss-pLG. These results suggest the significance of gelatin grafting, which probably allows gelatin to interact with the key residues of the amyloidogenic core of BSA effectively.

• Authors: Chelladurai Karthikeyan Balavigneswaran, Gaurav Kumar, Chandrasekaran Vignesh Kumar, Satheeshkumar Sellamuthu, Uvanesh Kasiviswanathan, Biswajit Ray, Vignesh Muthuvijayan, Sanjeev Kumar Mahto, Nira Misra
• Journal: Biopolymers (Biopolymers) Vol. 111 Issue 8 Pg. e23383 (Aug 2020) ISSN: 1097-0282 [Electronic] United States
• PMID: 32604473 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Amyloid
• Polyesters
• Protein Aggregates
• Serum Albumin, Bovine
• poly(lactide)
• Gelatin

Topics

• Amyloid (chemistry)
• Animals
• Cattle
• Gelatin (chemistry)
• Humans
• In Vitro Techniques
• Neuroblastoma (drug therapy, metabolism, pathology)
• Polyesters (chemistry, pharmacology)
• Protein Aggregates (drug effects)
• Serum Albumin, Bovine (antagonists & inhibitors, metabolism)
• Tumor Cells, Cultured