Cell mechanosensory recognizes ligand compliance at biomaterial interface

Area of Science:

• Biomaterials Science
• Cell Biology
• Mechanobiology

Background:

• Cells interact with the extracellular matrix (ECM) through ligand-receptor bonds, sensing mechanical properties.
• Cell receptors engage ligands, exerting pulling forces via focal adhesions (FAs).

Purpose of the Study:

• To develop and characterize functional peptide ligands with tuneable mechanical properties for surface adsorption.
• To investigate how ligand adsorption and mechanical resistance influence cell recognition, polarization, and FA formation.

Main Methods:

• Designed two-domain peptide ligands with ECM-derived and anchoring domains.
• Verified tuneable compliance of the anchoring domain using molecular dynamics and adsorption measurements.
• Assessed cell response (recognition, polarization, FA area) to ligands with varying adsorption and mechanical properties.

Main Results:

• Highest adsorbed peptides with integrin-binding motifs promoted cell recognition and polarization with larger mature FA areas.
• Lowest adsorbed sequences lacked mechanical resistance, resulting in rounded cells with smaller FA areas.
• Demonstrated that cells can discriminate ligands based on surface mechanical properties.

Conclusions:

• Ligand design for material bioactivation should consider mechanical properties to control cell-material interactions.
• Cell mechanosensing plays a critical role in how cells respond to surface-bound ligands.
• Tailoring ligand compliance is key for directing cell behavior and FA development.