Metrology of Biopreservation in Saccharide-Based Glasses using H-bond Network Lifetimes

 

Jerainne M. Johnson, Jitendra Sharma and Marcus T. Cicerone

 

With the advancement of the biotechnological industry the use of proteins in drug delivery and tissue engineering has rapidly increased. The need for stabilization of these protein-based systems has thus become of vital importance. For many applications, dry formulations are required, and the proteins are preserved by being embedded in saccharide-based glasses. It is thought that the dynamics of the glass matrix slow or suppress motions of the embedded protein, thus slowing physical and chemical degradation processes.

It has long been known that the a relaxation process alone cannot be used as a predictive measure for how well a glass will preserve a protein; inconsistencies arise when it is used alone.  Neutron scattering measurements of saccharide-based glasses demonstrate distinct correlation between the fast local dynamics of the glass and protein stability of model and therapeutic proteins. In addition, MD simulations on these glasses shows a direct relationship between neutron scattering and hydrogen-bond dynamics, where hydrogen-bond lifetimes and hydrogen occupation in the glasses, track the fast local dynamics observed in the neutron scattering measurements. These results imply that hydrogen-bond lifetimes may be a potentially suitable measure for determining stability in host glass matrices.

We have conducted experiments using a fluorescent dye that is sensitive to hydrogen-bond dynamics.  These studies confirm MD results that hydrogen bond dynamics impact stability. The studies also provide a simple bench-top methodology for evaluating host glass matrices for protein preservation.

 

Mentor name:              Marcus Cicerone

Division:                      Polymers

Laboratory:                 MSEL

Room and Building

address:                       106 B/224

Mail Stop:                   8543

Telephone #:                301-975-8595

FAX #:                        301-975-4977

email:                           jerinne.johnson@nist.gov

Sigma Xi member:      No

Category:                    Biotechnology, Chemistry