Cell migration through defined, synthetic extracellular matrix analogues

TLDR

Synthetic ECM analogues can serve as 3‑D platforms for mechanistic studies of cell migration. The study examines how adhesive ligand density influences fibroblast and smooth muscle cell migration in degradable hydrogels. Hydrogels are PEG diacrylate-based polymers with proteolytically degradable peptides in the backbone and adhesive peptides grafted to the network, enabling controlled ligand density and enzymatic degradation. Cell migration in these hydrogels occurs only when both adhesive ligands and proteolytic degradation are present, and migration is maximized at intermediate ligand densities, revealing a biphasic dependence.

Abstract

We have developed synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study mechanisms involved in cell migration, such as receptor-ligand interactions and proteolysis. The biomimetic hydrogels consist of bioinert polyethylene glycol diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesive peptide sequences grafted to the network. Hydrogels have been developed that degrade as cells secrete proteolytic enzymes. Adhesive peptide sequences grafted to the hydrogel provide ligands that can interact with receptors on the cell surface to mediate adhesion and spreading. In this study, we have characterized the effects of adhesive ligand density on fibroblast migration through collagenase-degradable and plasmin-degradable hydrogels and on smooth muscle cell migration through elastase-degradable hydrogels. In all three cases, we found that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. Furthermore, both adhesive and proteolytically degradable sequences were required for cell migration to occur. These synthetic ECM analogues may be useful for 3-D mechanistic studies of many aspects of cell migration