Glycocalyx disruption enhances motility, proliferation and collagen synthesis in diabetic fibroblasts

Impaired wound healing represents one of the most debilitating side effects of Diabetes mellitus. Though the role of fibroblasts in wound healing is well-known, the extent to which their function is altered in the context of diabetes remains incompletely understood. Here, we address this question by comparing the phenotypes of healthy dermal fibroblasts (HDFs) and diabetic dermal fibroblasts (DDFs). We show that DDFs are more elongated but less motile and less contractile than HDFs. Reduced motility of DDFs is attributed to formation of larger focal adhesions stabilized by a bulky glycocalyx, associated with increased expression of the cell surface glycoprotein mucin 16 (MUC 16). Disruption of the glycocalyx not only restored DDF motility to levels comparable to that of HDFs, but also led to increased proliferation and collagen synthesis. Collectively, our results illustrate the influence of glycocalyx disruption on mechanics of diabetic fibroblasts relevant to cell motility.