![]() Of course, it is important to recognize that the ECM deformations are being caused by the cell itself as a consequence of its own migration. When migratory cells do change directions, this change is preceded by a change in the local ECM strain field. Indeed, mesenchymal migration in fibrillar 3D matrices deviates from the persistent random walk (PRW) model (used to describe migration on 2D isotropic substrates) in that migration velocity is biased in the direction of cell alignment. Anisotropic ECM deformations precede directional protrusions and migration initiation in spreading cells, and are correlated with migration direction in migrating cells. Cell-mediated ECM fiber deformations by migratory cells are anisotropic-they are not uniformly distributed around the cell-and are correlated with localized protrusive activity. ![]() Several recent studies support the hypothesis that individual cells are capable of reorganizing the local ECM architecture sufficiently to affect their own migration. ), although not to the same extent as achieved by masses of cells. However, individual cells are also capable of increasing the alignment and density of ECM fibers locally as they migrate (e.g. This interplay between mesenchymal-like cell migration and fibrous ECM remodeling is typically observed and studied in the context of large numbers of cells invading matrices over several days and causing large-scale remodeling that is observable even under low magnification (e.g. Thus, this example of dynamic reciprocity illustrates a positive-feedback relationship: cells collectively generate directional cues (matrix remodeling) that reinforce their own migration (contact guidance, durotaxis), which in turn reinforces the cues. ) by restricting adhesions and protrusions and increasing local stiffness and adhesive sites in the direction of increased fiber alignment and density. This matrix remodeling in turn promotes directed cell migration (e.g. Cells invading from a tissue, tumor, or other localized placement into an unpopulated fibrous ECM cause widespread fiber alignment and densification (e.g. Ī major example of dynamic reciprocity in mesenchymal-like cell migration is the interplay between cell invasion and extracellular matrix (ECM) remodeling. cells and their environment exist in a state of “dynamic reciprocity” in which each affects and is affected by the other. However, it has long been known that cells are not only guided by these cues, but also play a substantial role in defining them, i.e. Numerous microenvironmental cues that determine the direction of cell migration have been identified including chemical, stiffness, adhesion, and magnetic gradients, cell contacts, contact guidance, and contact inhibition (see reviews: ). ![]() Finally, our results demonstrate that the bi-directional relationship between cell remodeling and migration is not a “dimensionality” effect, but a fundamental effect of fibrous substrate structure.Ī cell’s local environment (microenvironment) influences its migratory behavior-not only decisions about whether to migrate, but how to migrate and in which direction. Further experiments involving 2D collagen and electrospun polymer scaffolds suggest that substrates composed of rigid, randomly oriented fibers reduce cells’ ability to follow another directionality cue by forcing them to meander to follow the available adhesive area (i.e. We observed that the cells’ inability to align and condense fibers resulted in a decrease in persistence relative to cells in native collagen matrices and even relative to isotropic (glass) substrates. Our results demonstrate that this positive-feedback relationship is indeed a fundamental aspect of cell migration in fibrillar environments. ![]() In this study, we directly tested this hypothesis by studying the migration persistence of individual HT-1080 fibrosarcoma cells migrating in photocrosslinked collagen matrices with limited remodeling potential. While this positive-feedback relationship has been widely described for cells invading en masse, single cells are also able to align ECM fibers, as well as respond to contact guidance and durotaxis cues, and should therefore exhibit the same relationship. The forces generated by many migrating cells cause fiber alignment, which in turn promotes further migration in the direction of fiber alignment via contact guidance and durotaxis. This bi-directional relationship is seen in the alignment of extracellular matrix (ECM) fibers ahead of invading cell masses. However cells not only follow, but in many cases, also generate directionality cues by modifying their microenvironment. of a chemokine) or polarizing feature (e.g. Directed cell migration arises from cells following a microenvironmental gradient (e.g.
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