Hydrogels are a class of special materials that contain a large amount of water and behave like rubber.These materials have found broad applications in tissue engineering,cell culturing,regenerative medicine etc.Recently,the exploration of peptide-based supramolecular hydrogels has greatly expanded the repertoire of hydrogels suitable for biomedical applications.However,the mechanical properties of peptide-based hydrogels are intrinsically weak.Therefore,it is crucial to develop methods that can improve the mechanical stability of such peptide-based hydrogels.In this review,we explore the factors that determine or influence the mechanical stability of peptide-based hydrogels and summarize several key elements that may guide scientists to achieve mechanically improved hydrogels.In addition,we exemplified several methods that have been successfully developed to prepare hydrogels with enhanced mechanical stability.These mechanically strong peptide-based hydrogels may find broad applications as novel biomaterials.It is still challenging to engineer hydrogels in order to mimic the mechanical properties of biological tissues.More hydrogel materials with optimal mechanical properties suitable for various types of biological applications will be available in the near future.
Decorsin,an antagonist of integrin glycoprotein IIb/IIIa,contains Arg-Gly-Asp(RGD)sequence and three disulfide bridges.The function of RGD sequence has already been well defined,but the roles of conserved disulfide bonds in antihemostatic proteins still remain unclear.Herein we use the fusion expression and characterization of mutant decorsin to study the functions of disulfide bonds in protein structure,stability and biological activity.The purified protein shows an apparent inhibition of activity to platelet aggregation induced by ADP with IC50 of 500 nM.The removal of cys7-cys15(from cysteine to serine)at the N-terminal causes a thirty-fold decrease of the inhibition activity with IC50 of 15 M,whereas the mutation of cys22-cys38 at the C-terminal completely impairs the biological activity of decorsin.The overall secondary and tertiary structures of decorsin are disrupted inevitably without disulfide bonds.Using a domain insertion mutation,the retaining of RGD loop and the adjacent disulfide bond produces a week antihemostatic activity of decorsin.This reveals that the overall structure of decorsin stabilized by the three conserved disulfide bridges is cooperative for antihemostatic function.Our study on the effect of disulfide bonds together with RGD-sequence on the protein function is helpful for structure-based drug design of antithrombotic research.
