Title: Vascular Smooth Muscle Cell Response to Transglutaminase 2 Cross-linked Collagen Fibril Thin Films.


Authors: Tighe A. Spurlin, Kiran Bhadriraju, Koo-Hyun Chung, Alessandro Tona, and Anne L. Plant



Tissue transglutaminase 2 (TG2) is a ubiquitous protein thought to play an important role in both the normal and abnormal progression of the wound healing response through extracellular matrix (ECM) cross-linking. However, how TG2 cross-linking of ECM affects cell behavior is still ill-defined. Here we use a model ECM system to show that vascular smooth muscle cell (vSMC) spreading, proliferation, actin polymerization, and myosin activation increase with increasing exposure of type 1 collagen fibrils to TG2 activity. A10 vSMC ligate fibrillar type 1 collagen through beta(1) integrins, and beta(1) integrin ligation appeared to be identical before and after TG2 cross-linking of collagen. This result suggests that the observed changes in cell response were not induced by changes in surface chemistry or receptor recognition. Atomic force microscopy (AFM) studies show that untreated fibrils are more susceptible to lateral movement on the surface than cross-linked fibrils, which suggest that the observed cell response is solely due to TG2-induced changes in the mechanical properties of collagen fibrils. The results provide valuable insight into a mechanism by which TG2-modified ECM proteins can influence cell behavior.



Author: Tighe A. Spurlin

Mentor: Anne Plant

Division: 831

Category: Biology