Introduction and Objective: Diabetes Mellitus is strongly associated with vascular complications. While molecular mechanisms of hyperglycemia-induced vascular dysfunction have been extensively studied, the organization of mechanical forces within endothelial monolayers under sustained hyperglycemia remains poorly defined. We investigated whether prolonged hyperglycemia alters endothelial force organization over time.Methods: Human Umbilical Vein Endothelial Cells were cultured in normoglycemic (5 mM) or clinically relevant hyperglycemic (13.9 mM) conditions for 5, 8, 15, and 23 days. Cells were micropatterned onto 1.8 mm diameter islands on 1.2 kPa polyacrylamide substrates and imaged 24 hours later at 2-minute intervals for 1 hour. Traction force microscopy and monolayer stress microscopy quantified root mean square (RMS) traction and strain energy. Inter-island heterogeneity was assessed using trimmed coefficients of variation (CV).Results: At 5 days, hyperglycemia reduced inter-island heterogeneity relative to normoglycemia, trimmed CV_strain: 0.21 vs 0.63; trimmed CV_RMS: 0.11 vs 0.39, indicating enhanced mechanical coordination. At 8 days, heterogeneity modestly increased under hyperglycemia, CV_strain: 1.05 vs 0.64; CV_RMS: 0.63 vs 0.44. By 15 and 23 days, variability between groups was comparable.Conclusion: Sustained clinically relevant hyperglycemia is associated with endothelial mechanical organization in a time-dependent manner. Early exposure promotes coordinated mechanical behavior, whereas prolonged exposure does not produce uniform mechanical destabilization. These findings suggest altered mechanical organization represents an underrecognized systems-level feature of endothelial dysfunction in diabetes.
S. Scheller: None.
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