Title: Enhanced Mechanical Rigidity of Hydrogels Formed from Enantiomeric Peptide Assemblies

Authors: Katelyn J. Nagy†‡, Michael C. Giano†‡, Albert Jin§, Darrin J. Pochanǁ, and Joel P. Schneider†

Journal: Journal of the American Chemical Society

Affiliation: †National Cancer Institute, Center for Cancer Research; ‡University of Delaware, Department of Chemistry and Biochemistry; §National Institute of Biomedical Imaging and Bioengineering, Laboratory of Cellular Imaging and Macromolecular Biophysics; ǁUniversity of Delaware, Department of Materials Science

Hydrogels have a multitude of biologically relevant applications.  In this article the authors investigate how the chirality of the molecules can be used to further the usefulness of hydrogels.  Specifically, the authors are constructing self-assembling hydrogels from polypeptides.  Polypeptides are especially useful, because they can be degraded by proteolytic enzymes.  These enzymes are specific for the L-isomeric peptide, so the authors thought about controlling the degradation process by introducing the D-isomeric peptide.  However, while they were investigating this idea they discovered a “large, nonadditive, synergistic enhancement” of the stiffness of their hydrogels from the addition of D-isomeric polypeptide.  This is a great example of serendipitous science!

The authors use MAX1 a 20 amino acid peptide that self-assembles into a hydrogel upon increasing the ionic strength (adding salt).  In MAX1 all of the peptides are the L-isomeric form, but the authors also made DMAX1, the equivalent of MAX1, but using all D-isomeric peptides.  They found that DMAX1 also self assembles upon increasing the ionic strength just like MAX1.  They also found hydrogels of DMAX1 and MAX1 to have nearly identical mechanical properties.

The authors then made hydrogels using various ratios of MAX1 to DMAX1.  They found that a 1:1 mixture made a hydrogel with four times the rigidity than either the MAX1 or DMAX1 hydrogel.  Mixing in a 1:3 and 3:1 ratio produced hydrogels that were nearly identical to each other in mechanical properties, but had rigidity between that of the 1:1 hydrogel and a hydrogel of either pure enantiomer.

The authors also investigated whether this effect was just the product of the introduction of any sequence of peptide of opposite chirality.  The authors produced a sequence of polypeptide that had similar gelation and mechanical properties as DMAX1 and MAX1.  Upon making a 1:1 mixture of the control polypeptide and DMAX1 they found that it had no significant enhancement in rigidity.  The authors concluded that the relationship between DMAX1 and MAX1 is important in obtaining increased stiffness.

An explanation for the effect at the molecular level is not yet clear, but the authors did take Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM) images of the various hydrogels.  They found that the fibril structure of the enantiomerically pure hydrogels is similar to that of the mixtures.  With all of their data in hand the authors conclude that the increased rigidity is due to favorable energetic interactions of DMAX1 and MAX1.  They discuss various types of favorable interactions that are possible.  They are currently working to understand the relationship and we can look forward to more interesting articles about these hydrogels!

This paper demonstrates how chirality can be used to control hydrogel stiffness.  The authors imagine using “enantiomers, diastereomers, meso compounds, and racemates of self-assemblers to control the mechanistic pathways by which molecules assemble to produce novel shapes, network morphologies, and material properties.”