Collective Cell Migration in Embryogenesis Follows the Laws of Wetting

Abstract

Collective cell migration is a fundamental process during embryogenesis and its initial occurrence, called epiboly, is an excellent in vivo model to study the physical processes involved in collective cell movements that are key to understanding organ formation, cancer invasion, and wound healing. In zebrafish, epiboly starts with a cluster of cells at one pole of the spherical embryo. These cells are actively spreading in a continuous movement toward its other pole until they fully cover the yolk. Inspired by the physics of wetting, we determine the contact angle between the cells and the yolk during epiboly. By choosing a wetting approach, the relevant scale for this investigation is the tissue level, which is in contrast to other recent work. Similar to the case of a liquid drop on a surface, one observes three interfaces that carry mechanical tension. Assuming that interfacial force balance holds during the quasi-static spreading process, we employ the physics of wetting to predict the temporal change of the contact angle. Although the experimental values vary dramatically, the model allows us to rescale all measured contact-angle dynamics onto a single master curve explaining the collective cell movement. Thus, we describe the fundamental and complex developmental mechanism at the onset of embryogenesis by only three main parameters: the offset tension strength, α, that gives the strength of interfacial tension compared to other force-generating mechanisms; the tension ratio, δ, between the different interfaces; and the rate of tension variation, λ, which determines the timescale of the whole process.

Heterogeneity of calcium clock functions in dormant, dysrhythmically and rhythmically firing single pacemaker cells isolated from SA node

“…Our finding of different functional cell populations isolated from SA node may corroborate, at least in part, these prior findings concerning different firing rate of parts (pieces or slices) of the SA node [19,20]. Recent recording of Ca 2+ in the intact mouse SA node using high-resolution cameras also indicate that some HCN4 positive cells within the intact SA node do generate LCRs, but do not generate APs, with the SAN generating normal physiological rhythm at its exits [24]. Those cells in the intact SA node are similar to the isolated dormant cells described in the present study (many of them also HCN4-positive, see Fig.…”

Active wetting of epithelial tissues

“…To understand the nature of these physical properties and their impact on tissue shape, extensive research has focused on how a three-dimensional cell aggregate spreads on a substrate [4][5][6][7][8] . Besides mimicking biological processes such as epiboly in zebrafish [9][10][11][12] , the spreading of a cell aggregate is amenable to theoretical and experimental access, and has become a widespread model process.…”

Surface and Bulk Stresses Drive Morphological Changes in Fibrous Microtissues

“…During embryonic development or in 3D in vitro cell aggregate cultures, surface tension can drive morphological transitions such as viscous spreading, cell sorting, and fusion of microtissues (27,(51)(52)(53). In these biological systems, the surface tension is determined by intercellular adhesion and cortical tension (29).…”