Focal adhesion clustering drives endothelial cell morphology on patterned surfaces

Area of Science:

• Biomaterials Science
• Cell Biology
• Vascular Biology

Background:

• Endothelial cell (EC) shape and alignment are critical for vascular function and disease development, particularly near blood flow disturbances.
• Current in vitro models show ECs are sensitive to substrate properties, but mechanisms regulating their morphology and orientation remain unclear.
• Substrate patterning, using adhesive motifs or topography, influences EC behavior, yet direct comparisons of their effects are limited.

Purpose of the Study:

• To investigate how endothelial cells perceive and respond to patterned bio-adhesive versus microgrooved topographic surfaces with identical feature dimensions.
• To elucidate the underlying cellular mechanisms, specifically focal adhesion clustering and cytoskeletal organization, that govern EC morphology and orientation on different patterned substrates.
• To provide insights for designing improved biomaterials for cardiovascular devices.

Main Methods:

• Fabrication of patterned surfaces with identical feature dimensions, comprising planar bio-adhesive motifs and microgrooved topographies.
• Culturing of endothelial cells on these distinct patterned substrates.
• Microscopic analysis to assess EC morphology, orientation, and focal adhesion distribution.

Main Results:

• Both patterned bio-adhesive and microgrooved surfaces effectively guided and directed EC orientation.
• Endothelial cells exhibited significantly greater elongation on patterned bio-adhesive surfaces compared to microgrooved surfaces.
• Focal adhesion clustering was identified as the key regulatory factor for EC morphology, subsequently driving cytoskeletal organization.

Conclusions:

• Substrate topography and adhesive patterning differentially regulate endothelial cell elongation.
• Focal adhesion dynamics are central to mechanotransduction, controlling EC shape and cytoskeletal organization in response to surface cues.
• Findings can inform the design of advanced biomaterials for enhancing the performance of implantable cardiovascular devices.