December 8, 2007 | David F. Coppedge

What Keeps Skin Strong? Velcro!

Skin would fall to pieces were it not for velcro-like molecules that bind its cells together.  These molecules, called cadherins, make skin strong but also supple.  Their secret was explained by Ashraf Al-Amoudi of the European Molecular Biology Laboratory, quoted in Live Science.  “The trick is that each cadherin binds twice: once to a molecule from the juxtaposed cell and once to its next-door neighbor.  The system works a bit like specialized Velcro and establishes very tight contacts between cells.
    Al-Amoudi, Achilleas Frangakis and two others achieved a first: an image of skin cells using cryo-electron tomography.  By taking images at different angles, this technique allows construction of a 3-D image of the subject.  A color-coded reconstruction of a skin cell and its tightly-packed organelles accompanies the article.  A similar report on Science Daily shows an image of how the cadherin molecules interact.
    The original paper in Nature provides more details about how cadherins link up.1  In skin, the proteins are parts of structures called desmosomes, which not only provide adhesion, but “encode instructions to drive tissue morphogenesis [structure formation] and to regulate tissue homeostasis [dynamic equilibrium].”  When seen for the first time via cry-electron tomography, the structure of the desmosomes, previously thought to be rather chaotic, came to light: “Our results indicate that the molecules interact at the midline, forming building blocks of alternate cis [same-side] and trans [alternate-side] dimers [proteins consisting of two domains], and thus resulting in a highly packed regular organization.”  They called this interaction a “zipper-like organization” of the cadherin molecules.  “Despite the quasi-periodicity of the cadherin arrangement, the cadherins retain a significant flexibility without losing their alternating interaction pattern.
    Even more fascinating than the structure is how it is assembled in an orderly sequence:

Even though the images are static, our results support the hypothesis that desmosomal cadherins on the cell surface are first clustered into small groups interacting through specific residues in the EC1 domains to form cis homodimers.  The opposing cell membranes are then brought in close proximity to enable the formation of the trans homodimers, which relies on Trp 2 and the hydrophobic pocket together with residues involved in molecular specificity.  Once the initial recognition is established, more molecules are brought to the contact zone, thus compacting the junction.  This compaction process is regularized by building blocks of alternate cis and trans dimers so that the strength of cell-cell contact is homogeneous.  These processes are repeated to extend the junction and finally form the fully mature desmosome.

The authors made no mention of how this structural arrangement might have evolved.  Cadherins are also used in heart muscle – a tissue that really depends on having reliable yet flexible adhesion.

1.  Al-Amoudi, Diez, Betts and Frangakis, “The molecular architecture of cadherins in native epidermal desmosomes,” Nature 450, 832-837 (6 December 2007) | doi:10.1038/nature05994.

There’s more going on in your outer layer than you can possibly imagine.  The beauty of biological organization is not just skin deep.  Skin deep is only where it starts.  And realize that the skin tissue itself is the easy part; skin is also filled with sensors, communication channels and other wonders that bear witness to wise planning and intelligent organization.  That’s why these scientists, like many others reporting on real lab work, seemed to have no need or use for evolutionary explanations.

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Categories: Amazing Facts, Human Body

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