Extracellular matrix type modulates cell migration on mechanical gradients

Abstract

Extracellular matrix composition and stiffness are known to be critical determinants of cell behavior, modulating processes including differentiation, traction generation, and migration. Recent studies have demonstrated that the ECM composition can modulate how cells migrate in response to gradients in environmental stiffness, altering a cell’s ability to undergo durotaxis. These observations were limited to single varieties of extracellular matrix, and typically cells are exposed to environments containing complex mixtures of extracellular matrix proteins. Here, we investigate migration of NIH 3T3 fibroblasts on mechanical gradients coated with one or more type of extracellular matrix protein. Our results show that NIH 3T3 fibroblasts exhibit durotaxis on fibronectin-coated mechanical gradients but not on those coated with laminin, demonstrating that extracellular matrix type can act as a regulator of cell response to mechanical gradients. Interestingly, NIH 3T3 fibroblasts were also observed to migrate randomly on gradients coated with a mixture of both fibronectin and laminin, suggesting that there may be a complex interplay in the cellular response to mechanical gradients in the presence of multiple extracellular matrix signals. These findings indicate that specific composition of available adhesion ligands is a critical determinant of a cell’s migratory response to mechanical gradients.

Role of Extracellular Matrix in Development and Cancer Progression

“…The speed of migration is also influenced by the composition of the ECM. Hartman et al [ 95 ] have shown that fibroblasts cultured in rigidity gradients composed of fibronectin exhibited cell migration while those cultured on matrices covered with either laminin or a fibronectin/laminin mixture did not exhibit any migration. These results indicate that the ECM not only serves as a track for migration, but also dictates cell migration due to its mechanical properties.…”

Human Atrial Fibroblast Adaptation to Heterogeneities in Substrate Stiffness

“…A model allowing the introduction of spatial gradients in the mechanical properties has been used to show that the stiffness-guided migration of fibroblasts, a process called durotaxis, depends on the type of matrix proteins (Hartman et al, 2017). Further, hydrogels with micropatterned stiff and soft areas were used to show adaptation of cell spreading over a wide range of stiffnesses (Sunyer et al, 2012) and to study the role of matrix organization for mesenchymal stem cell differentiation (Yang et al, 2016).…”

Engineering the cellular mechanical microenvironment – from bulk mechanics to the nanoscale

“…In particular, laminin inhibits durotaxis even when mixed with other proteins that promote it (e.g. fibronectin) (Hartman et al, 2017).…”