Mechanical Intercellular Communication via Matrix-Borne Cell Force Transmission During Vascular Network Formation

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Intercellular communication is vital for tissue formation and function.
• Mechanical communication via cell-generated forces through the extracellular matrix (ECM) is not fully understood.
• Endothelial cells (ECs) form critical vascular networks.

Purpose of the Study:

• To investigate mechanical intercellular communication (MIC) in endothelial cell (EC) assembly.
• To elucidate the role of cell-generated forces and ECM mechanics in network formation.
• To explore the contribution of calcium signaling to MIC and vessel-like network assembly.

Main Methods:

• Utilized mechanically defined, synthetic electrospun fibrous matrices.
• Employed microfabrication-based cell patterning for ECs.
• Investigated ECs within deformable fibrous matrices and fibrin hydrogels.

Main Results:

• Cell force-mediated matrix displacements drive directional EC extension and migration prior to cell-cell connection.
• Vascular endothelial cadherin (VE-cadherin) is enriched in stable cell-cell connections.
• Calcium signaling, focal adhesion kinase, and mechanosensitive ion channels are critical for MIC.
• MIC extends to the multicellular assembly of 3D vessel-like networks in fibrin hydrogels.

Conclusions:

• Cell-generated forces and ECM mechanical properties are key to assembling capillary-like EC networks.
• MIC plays a significant role in multicellular assembly.
• Findings motivate the development of biomaterials that enhance MIC for vascular tissue engineering.