Subendothelial stiffness alters endothelial cell traction force generation while exerting a minimal effect on the...

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Endothelial cells are sensitive to their mechanical environment.
• Subendothelial stiffness influences endothelial cell migration and mechanics.
• The role of transcriptional reprogramming in these responses is unclear.

Purpose of the Study:

• To investigate the impact of subendothelial stiffness on endothelial cell mechanics and gene expression.
• To determine if transcriptional changes underlie the biomechanical response to stiffness.
• To compare responses between primary human umbilical vein endothelial cells (HUVEC) and immortalized human microvascular endothelial cells (HMEC-1).

Main Methods:

• Measurement of endothelial cell traction force generation.
• Gene expression profiling (transcriptome analysis).
• Culture of HUVEC and HMEC-1 on soft versus stiff matrices.

Main Results:

• Both HUVEC and HMEC-1 increased traction stresses on stiffer matrices.
• Transcriptome analysis revealed minimal stiffness-dependent gene expression changes.
• Few differentially expressed genes were found, and none were shared between cell types.
• HUVEC, but not HMEC-1, upregulated TGF-β2 on stiffer matrices and responded to exogenous TGF-β2.

Conclusions:

• Subendothelial stiffness significantly alters endothelial cell mechanics.
• The conserved biomechanical response to stiffness is largely independent of transcriptional reprogramming.
• Endothelial cell responses to stiffness involve post-transcriptional or post-translational modifications rather than widespread gene expression changes.