Fig. 4.

Schematic drawing of cell-matrix interactions in health and disease. Center: cell in normal conditions interacting via integrins with surrounding ECM, which in vivo typically exhibits some tension. Bottom row shows typical behavior of tissue equivalents developing a homeostatic nonzero plateau of tension over time. Right: In case of further increases in tension, i.e., overloading, healthy tissue seeks to restore the prior mechanical state due to a homeostatic feedback loop consisting of mechanosensation, mechanotransduction, and mechanoregulation. If this feedback loop is compromised, pathological signaling can lead to a fibrotic response (top right). In general, both the healthy and the fibrotic reaction may help to restore the preferred mechanical state (bottom right). Left: in case of decreases in tension, i.e., under-loading, e.g., due to injury, homeostatic feedback loops can lead to re-establishment of a homeostatic state. By contrast, pathological mechanosensitivity of tissues can lead to apoptosis (top row). The homeostatic feedback loop aims at restoring the homeostatic state, whereas apoptosis may lead to tissue failure (bottom row)