Differential adhesion hypothesis (DAH) is a

hypothesis A hypothesis (plural hypotheses) is a proposed explanation for a phenomenon. For a hypothesis to be a scientific hypothesis, the scientific method requires that one can testable, test it. Scientists generally base scientific hypotheses on prev ...

that explains cellular movement during

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

with thermodynamic principles. In DAH tissues are treated as liquids consisting of mobile cells whose varying degrees of surface adhesion cause them to reorganize spontaneously to minimize their interfacial free energy. Put another way, according to DAH, cells move to be near other cells of similar adhesive strength in order to maximize the bonding strength between cells and produce a more thermodynamically stable structure. In this way the movement of cells during tissue formation, according to DAH, parodies the behavior of a mixture of liquids. Although originally motivated by the problem of understanding cell sorting behavior in vertebrate embryos, DAH has subsequently been applied to explain several other morphogenic phenomena.

Background

The origins of DAH can be traced back to a 1955 study by

Philip L. Townes Philip Leonard Townes (February 18, 1927 – April 1, 2017) was an American physician, human geneticist, embryologist and developmental biologist who identified Townes–Brocks syndrome (along with Eric Brocks) in 1972 while a Professor of Pediatri ...

and

Johannes Holtfreter Johannes Holtfreter (January 9, 1901 – November 13, 1992) was a German-American developmental biologist whose primary focus was the “organizer,” a part of the embryo essential for the development of the proper body plan. Biography Holtfr ...

. In this study Townes and Holtfreter placed the three

germ layer A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three pr ...

s of an amphibian into an alkaline solution, allowing them to dissociate into individual cells, and mixed these different types of cells together. Cells of different species were used to be able to visually observe and follow their movements. Cells of similar types migrated to their correct location and reaggregated to form germ layers in their developmentally correct positions. This experiment demonstrated that tissue organization can occur independent of the path taken, implying that it is mediated by forces that are persistently present and doesn't arise solely from the chronological sequence of developmental events preceding it. From these results Holtfreter developed his concept of selective affinity, and hypothesized that well-timed changes to selective affinity of cells to one another throughout development guided morphogenesis. Several hypotheses were introduced to explain these results including the "timing hypothesis" and the "differential surface contraction hypothesis". In 1964 Malcolm Steinberg introduced the "differential adhesion hypothesis" which uses thermodynamic principles to describe and explain patterns of cell sorting and arrangement observed.

Overview

According to DAH, cellular movement and assortment is governed by the spontaneous rearrangement of cells—in much the same way as a liquid—to a more thermodynamically stable equilibrium. This is achieved by maximizing the amount of energy that is utilized adhering the cells together, which decreases the free energy available in the system. As cells with similar strengths of surface adhesion bond to one another, bonding energy in the overall system increases, and interfacial free energy decreases causing the system to be more thermodynamically stable. Liquids behave in a comparable manner, but with molecules moving around due to

kinetic energy In physics, the kinetic energy of an object is the energy that it possesses due to its motion. It is defined as the work needed to accelerate a body of a given mass from rest to its stated velocity. Having gained this energy during its a ...

instead of motile cells moving around due to a combination of their kinetics and active movement. This allows examples of tissue arrangement to be corresponded to the behavior of liquids, such as one tissue spreading across another being corresponded to oil spreading across water; the oil spreads across the water to minimize weak oil-water interactions and maximize stronger water-water and oil-oil interactions, the cells similarly sort themselves to be near other cells of similar adhesive strength and bond with them. Other tissue interactions that DAH offers an explanation for includes tissue hierarchy, where tissues with weaker surface adhesion surround tissues with stronger surface adhesion, the rounding of irregular cell masses to become spherical, and the cell sorting and construction of anatomical structures that occurs independent of the path taken. DAH does not rely on qualitative differences in cell adhesion, only on quantitative differences in the strength of their surface adhesion. DAH has been supported experimentally and by computational models.

Applications

Since its original formulation in the context of vertebrate embryogenesis, DAH has been utilized to offer an explanation for several other morphogenic phenomena including

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier aga ...

, and epithelial-mesenchymal transition in cancer progression and

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

References

{{reflist Cell adhesion Developmental biology Biological hypotheses

Background

Overview

Applications

See also

References