Dynamic cell–cell adhesion mediated by pericellular matrix interaction – a hypothesis

Abstract

Cell-cell adhesion strength, measured as tissue surface tension, spans an enormous 1000-fold range when different cell types are compared. However, the examination of basic mechanical principles of cell adhesion indicates that cadherin-based and related mechanisms are not able to promote the high-strength adhesion experimentally observed in many late embryonic or malignant tissues. Therefore, the hypothesis is explored that the interaction of the pericellular matrices of cells generates strong adhesion by a mechanism akin to the self-adhesion/self-healing of dynamically cross-linked hydrogels. Quantitative data from biofilm matrices support this model. The mechanism links tissue surface tension to pericellular matrix stiffness. Moreover, it explains the wide, matrixfilled spaces around cells in liquid-like, yet highly cohesive, tissues, and it rehabilitates aspects of the original interpretation of classical cell sorting experiments, as expressed in Steinberg's differential adhesion hypothesis: that quantitative differences in adhesion energies between cells are sufficient to drive sorting.

Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula

“…Assuming that this is the main component of γ r , and with a tip cell width of 40 µm, a force of 8-24 nN/cell would have to be resisted to maintain attachment, which could be achieved by 150-450 cadherin bonds. The maximal possible link tension for cadherin-mediated adhesion is 200 nN/cell (Winklbauer, 2019), which is an order of magnitude higher than the value calculated for tip cells.…”

Exploiting differential effects of actomyosin contractility to control cell sorting among breast cancer cells

“…Although integrins are typically thought of as mediating cell–ECM contacts and not cell–cell contacts, there are reports of strong integrin-based cohesion in cells. Reportedly, integrin-based adhesions can even be stronger than cadherin-based ones ( Foty and Steinberg, 2004 ; Winklbauer, 2019 ). Specifically, α 5 β 1 integrin has been shown to play a significant role in tissue cohesion through intercellular fibronectin adhesion ( Robinson et al.…”

Distribution and propagation of mechanical stress in simulated structurally heterogeneous tissue spheroids

“…This limits the applicability of the model predictions to immature artificial spheroids and early developmental structures, where the pericellular matrix is absent or sufficiently thin to justify its exclusion. 45 Future developments that take into account the contribution of the aforementioned phenomena in a similar modeling strategy will allow the quantification of mechanical effects due to tissue dynamics, and of changes in the mechanical microenvironment during tissue maturation.…”