Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases

Area of Science:

• Biomaterials Science
• Cell Biology
• Neuroscience

Background:

• Schwann cells (SCs) are crucial for nerve regeneration, exhibiting plasticity in response to injury.
• The extracellular matrix (ECM) and cell morphology critically regulate SCs during nerve repair.
• The specific roles of ECM mechanotransduction in SC phenotype remain largely unexplored.

Purpose of the Study:

• To investigate how matrix stiffness and cell morphology influence SC phenotype specification.
• To elucidate the involvement of mechanotransducers YAP/TAZ and RhoA in these processes.
• To understand the signaling pathways regulating SC regenerative capacity.

Main Methods:

• Utilized engineered microenvironments to precisely control ECM stiffness, cell shape, and cell spreading.
• Analyzed the activation of key mechanotransducers including YAP/TAZ, RhoA, and Rac1/MKK7/JNK.
• Quantified the expression of SC regenerative-associated proteins.

Main Results:

• Increased ECM stiffness and SC spreading downregulated SC regenerative proteins via RhoA and YAP/TAZ activation.
• Cell elongation promoted SC regenerative capacity by upregulating Rac1/MKK7/JNK signaling.
• Demonstrated a direct link between ECM properties, cell morphology, and SC regenerative potential.

Conclusions:

• ECM stiffness and cell morphology significantly modulate Schwann cell phenotype and regenerative capacity.
• Mechanotransduction pathways involving YAP/TAZ, RhoA, and Rac1/MKK7/JNK are key regulators.
• Findings provide critical insights for designing advanced biomaterials and cellular therapies for peripheral nerve regeneration.