Transglutaminase enzymes are ubiquitous Ca²⁺-dependent enzymes which catalyze the formation of crosslinks between glutamine and lysine resides of proteins.  Extensive transglutaminase-mediated crosslinking of soluble proteins is believed to be responsible for rapid physical gelation of certain biological fluids.  A common biological strategy for regulating the activity of transglutaminase enzymes is control of intracellular and extracellular Ca²⁺ concentration, mediated by lipid bilayer membranes.  Stimuli-responsive synthetic lipid vesicles offer a unique opportunity to regulate transglutaminase-mediated gelation by sequestering and then releasing enzyme-activating ion such as Ca²⁺.  Ca²⁺ release from light sensitive liposomes can be used to trigger TG-mediated crosslinking of proteins to form hydrogels suitable for the purpose of wound healing, drug delivery, and tissue engineering.  Natural proteins and synthetic polypeptides determined to be transglutaminase substrates are under investigation, in combination with Factor XIII and tissue transglutaminase, to formulate solutions which undergo rapid gelation upon activation of the enzyme by exposure to Ca²⁺.  (Collaborative project with Prof. Phillip B. Messersmith, Northwestern University, Division of Biological Materials).

Biomedical Applications : Skeletal Tissue Repair, Drug Delivery, Wound Healing, Tissue Reconstruction.

Photostimulated crosslinking of proteins via activation of Ca2+-dependent transglutaminase (TG) is an application of "cascade" triggering using photocatalytic diplasmenylcholine liposomes (see Triggerable Drug Delivery section)