Tissue cohesion and the mechanics of cell rearrangement

Abstract

Morphogenetic processes often involve the rapid rearrangement of cells held together by mutual adhesion. The dynamic nature of this adhesion endows tissues with liquid-like properties, such that largescale shape changes appear as tissue flows. Generally, the resistance to flow (tissue viscosity) is expected to depend on the cohesion of a tissue (how strongly its cells adhere to each other), but the exact relationship between these parameters is not known. Here, we analyse the link between cohesion and viscosity to uncover basic mechanical principles of cell rearrangement. We show that for vertebrate and invertebrate tissues, viscosity varies in proportion to cohesion over a 200-fold range of values. We demonstrate that this proportionality is predicted by a cell-based model of tissue viscosity. To do so, we analyse cell adhesion in Xenopus embryonic tissues and determine a number of parameters, including tissue surface tension (as a measure of cohesion), cell contact fluctuation and cortical tension. In the tissues studied, the ratio of surface tension to viscosity, which has the dimension of a velocity, is 1.8 µm/min. This characteristic velocity reflects the rate of cell-cell boundary contraction during rearrangement, and sets a limit to rearrangement rates. Moreover, we propose that, in these tissues, cell movement is maximally efficient. Our approach to cell rearrangement mechanics links adhesion to the resistance of a tissue to plastic deformation, identifies the characteristic velocity of the process, and provides a basis for the comparison of tissues with mechanical properties that may vary by orders of magnitude.

Cell adhesion strength from cortical tension – an integration of concepts

“…In Xenopus gastrula cells, the intensity of staining of the fluorescently labeled F-actin cortex diminishes within minutes of contact during re-aggregation (David et al, 2014). To be consistent with these observations, the high cortex density at the surface relative to its lower density at internal cell-cell borders in zebrafish gastrula explants (Krieg et al, 2008) and MDCK cell sheets (Reffay et al, 2014) should not be interpreted as an upregulation of cortex density at the tissue surface, but instead as its downregulation at internal cell contacts to promote adhesion.…”

“…To be consistent with these observations, the high cortex density at the surface relative to its lower density at internal cell-cell borders in zebrafish gastrula explants (Krieg et al, 2008) and MDCK cell sheets (Reffay et al, 2014) should not be interpreted as an upregulation of cortex density at the tissue surface, but instead as its downregulation at internal cell contacts to promote adhesion. Cell adhesion is, within limits, proportional to cadherin expression levels (Foty and Steinberg, 2005;Krieg et al, 2008), and in aggregating Xenopus gastrula cells, the reduced cortex density at cell-cell contacts is indeed inversely related to experimentally manipulated cadherin levels -decreased cadherin expression leads to lowered adhesion and increased cortex density at contacts, and increased cadherin expression has the opposite effects (David et al, 2014).…”

“…At the lower end of the scale, a tissue surface tension of 0.05 mJ/m 2 is found for the Xenopus gastrula endoderm (David et al, 2014). Mesodermal and ectodermal tissues from Xenopus, Rana and zebrafish gastrulae also have low tissue surface tensions, ranging from 0.15 to 0.8 mJ/m 2 (Davis et al, 1997;Schötz et al, 2008;David et al, 2014).…”

“…More recently, however, experimental findings (Krieg et al, 2008) and theoretical considerations (Brodland and Chen, 2000;Manning et al, 2010) rehabilitated Harris' original conjecture with a modification -instead of treating contractility as an alternative mechanism, it is described to act together with adhesion to determine the mutual attachment of cells. A further, crucial challenge to our conventional concept of adhesion came with the recognition that the binding energies of adhesion molecules are too small to account for the observed degrees of cell-cell attachment (Youssef et al, 2011;Maître et al, 2012;Amack and Manning, 2012;Stirbat et al, 2013;David et al, 2014).…”

Hücre içi trafik ve hücre davranış özellikleri

“…Kortikal aktin, blastosist yapısında yüzeydeki hücrelerde yoğun olarak bulunurken, iç hücre kitlesinde düşük yoğunlukta bulunur. Miyozin II aktin molekülllerine destek olarak iki bölgede de bulunurlar (27).…”