Fibronectin Peptide Modified Hydrogels Activate a Contractile Phenotype in Nucleus Pulposus Cells

Area of Science:

• Biomaterials Science
• Cell Biology
• Biochemistry

Background:

• Degenerative disc disease (DDD) is a primary cause of low back pain and disability.
• Aging and injury induce extracellular matrix (ECM) remodeling in the nucleus pulposus (NP), leading to stiffening and altered mechanical properties.
• Increased fibronectin deposition in DDD is linked to altered cellular adhesion and inflammatory signaling, but specific domains and their effects on cell phenotype remain unclear.

Purpose of the Study:

• To investigate how specific fibronectin domains influence cell phenotype in NP cells.
• To elucidate the role of fibronectin-integrin interactions in DDD pathogenesis.
• To develop a hydrogel system for controlled presentation of fibronectin domains.

Main Methods:

• Utilized a dextran vinyl sulfone (DexVS) hydrogel system to present specific fibronectin domains.
• Incorporated fibronectin peptides into the hydrogels for targeted interactions with integrin receptors.
• Assessed YAP signaling, NF-κB signaling, cellular adhesion, contractility, and aggrecan gene expression in NP cells.

Main Results:

• Fibronectin peptides significantly enhanced YAP and NF-κB signaling pathways in NP cells.
• These peptides increased cellular adhesion and contractility while decreasing aggrecan gene expression.
• Specific integrin-binding peptides from fibronectin were identified as activators of a contractile NP cell phenotype.

Conclusions:

• Fibronectin's integrin-binding domains play a critical role in activating a contractile phenotype in NP cells.
• Targeted modulation of fibronectin-integrin interactions using biomaterials can influence NP cell behavior.
• Understanding these mechanisms offers potential therapeutic strategies for degenerative disc disease.