Haptotaxis is cell type specific and limited by substrate adhesiveness.

Area of Science:

• Cell biology
• Biomaterials science
• Tissue engineering

Background:

• Motile cells use extracellular matrix (ECM) cues like ligand density and stiffness for navigation.
• Mesenchymal stem cells (MSCs) and fibroblasts encounter haptotactic gradients at tissue interfaces during migration.
• Understanding cell migration in response to ECM gradients is crucial for tissue repair and regeneration.

Purpose of the Study:

• To investigate how tunable RGD and collagen gradients in hydrogels regulate fibroblast and MSC migratory behaviors.
• To elucidate the role of cell-substrate adhesion and contractility in haptotaxis.
• To compare the haptotactic responsiveness of fibroblasts and MSCs.

Main Methods:

• Development of tunable RGD and collagen gradients in polyacrylamide hydrogels using density gradient multilayer polymerization (DGMP).
• Assessment of haptotaxis in mouse 3T3 fibroblasts and human MSCs under varying ligand concentrations and adhesion conditions.
• Measurement of cell contractility and substrate deformation.

Main Results:

• 3T3 fibroblasts exhibited haptotaxis independent of ligand composition and fiber deformation.
• Human MSCs demonstrated haptotaxis only when cell-substrate adhesion was reduced by soluble matrix ligand mimetic peptides.
• MSCs showed higher contractility than fibroblasts, and increased ligand concentration inhibited 3T3 fibroblast haptotaxis.

Conclusions:

• Haptotactic cell migration is influenced by cell-substrate adhesion levels.
• Fibroblasts appear more responsive to ligand gradients than MSCs for tissue homing and repair.
• Modulating cytoskeletal assembly was ineffective in promoting MSC haptotaxis.