Detachment and fracture of cellular aggregates

Abstract

The dynamics of cellular adhesion and deadhesion, which play key roles in many cellular processes, have most often been studied at the scale of single bonds or single cells. However, multicellular adhesion and deadhesion are also central processes in tissue mechanics, morphogenesis, and pathophysiology, where collective tissue phenomena may introduce additional effects that are absent at the single-cell level. In this paper we present experiments on the adhesion of cellular aggregates and a laboratory model system to study tissue mechanics. We introduce a technique to measure the forces and energies involved in the detachment of an aggregate from a substrate (which can be viewed as a cellular tack assay) and in the fracture between two partially fused aggregates, as a function of the adhesion time, the pulling speed, and the cadherin density at the cell surface. We develop a model based on polymer physics to interpret the observations. We identify a significant contribution to the adhesion energy of viscous dissipation mechanisms present at the tissue scale that are absent at the single-cell level, as well as a significant effect of the speed at which the separation force is applied.

Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex

“…In cultured suspended monolayers, the first power law phase had an exponent ~ 0.30, consistent with previous reports for cell aggregates subjected to compression 55 , and was present even when ATP was depleted. Given the clear dependence of the second phase of relaxation on ATP, we focused on the contributions of subcellular structures known to play a role in cell and tissue mechanics such as the adherens junctions 14,56,57 , desmosomes 58 , intermediate filaments 59,60 and actomyosin 14,[61][62][63][64][65] . Stress relaxation within cytoskeletal and adhesive structures likely stems from molecular turnover of their constituents 66 .…”

Multiparametric Analysis of Tissue Spheroids Fabricated from Different Types of Cells

“…Additionally, it is accepted that mechanical properties of TS strongly influence their fusion dynamics. [ 1 ] Different methods for their mechanical properties measurement exists: atomic force microscopy [ 58,59 ] and micropipette aspiration, [ 58,60 ] aggregate centrifugation, [ 58,61–63 ] aggregate detachment and fracture, [ 64 ] parallel microfiltration method. [ 65 ] The estimation of electro‐conductivity and electric impedance is a good example for indirect non‐invasive high‐throughput approach.…”

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

“…During the separation of adherent cells by an applied force, most of the work is dissipated in a transient deformation of cells and adhesion molecules (Décavé et al, 2002;Gonzalez-Rodriguez et al, 2013), but some is stored as free energy that is able to drive the re-adhesion of cells. This free energy per unit area, or tissue surface tension σ, is a suitable indicator of adhesion strength as it does not depend on the specifics of the separation process, for example on its rate.…”