The treatment of collagen fibrils by tissue transglutaminase to promote vascular smooth muscle cell contractile signaling.
The enzyme tissue transglutaminase 2 (TG2) appears to play an important role in several physiological processes such as wound healing, the progression of cancer and of vascular disease. Additionally, TG2 has been proposed as a means of stabilizing collagen extracellular matrix (ECM) scaffolds for tissue engineering applications. In this report, we examined the effect of TG2 treatment on the mechanical properties of the ECM, and associated cell responses. Using a model ECM of fibrillar collagen, we quantitatively examined vascular smooth muscle cell (vSMC) response to untreated, or TG2 treated collagen. We show that cells respond to TG2 treated collagen with increased spreading, an increase in contractile response as indicated by elevated F-actin polymerization and myosin light chain phosphorylation, and increased proliferation, without apparent changes in integrin specificity or matrix topography. Comparative atomic force microscopy loading studies indicate that TG2 treated fibrils are 3 times more resistant to shearing force from an AFM tip than untreated fibrils. The data suggest that TG2 treatment of collagen increases matrix mechanical stiffness, which apparently alters the contractile and proliferative response of vSMC.
Spurlin
Tighe A
TA
Biochemical Science Division, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899, USA. tighe.spurlin@nist.gov
Bhadriraju
Kiran
K
Chung
Koo-Hyun
KH
Tona
Alessandro
A
Plant
Anne L
AL
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D024022:Fibrillar Collagens / Q000737:chemistry*; D019204:GTP-Binding Proteins; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D011503:Transglutaminases / Q000008:administration & dosage* / Q000737:chemistry
D024022:Fibrillar Collagens; C000717609:Tgm2 protein, rat; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins