Generation of Controllable Gradients in Cell Density

摘要

Gradients in cell types, cell quantities, and extracellular-matrix (ECM) molecules represent a common feature of many biological systems. At the junction of non-mineralized and mineralized tissues in the tendon-to-bone insertion, for example, the cell phenotype gradually changes from fibroblasts in the tendon to fibrochondrocytes at the interface and osteoblasts in the bone. Similar gradations also exist at the myotendinous junction and between various tissue layers that make up the skin. These gradients in cell density regulate both quantity and quality of cell-cell interactions and thus the functions of relevant tissues. In a sense, the gradients determine the number of physical connections that a single cell is able to establish with surrounding cells, which in turn regulates cell behavior by influencing the intracellular signaling pathways. The perturbation of cell-cell interactions, as typically occurs during an injury, triggers a cascade of events that either re-establishes tissue homeostasis or, more often, leads to scar formation. In addition to physical connections, spatial variations in cell density may lead to the establishment of gradations in biochemical or ECM cues, as a result of which cell migration, proliferation, and differentiation can all be affected.171 As a result, the ability to generate controllable gradients in cell density is critical to the recreation of functionality for many types of tissues.