The mechanism that allows skin cells to sense change in their environment, Skin is our body’s most ardent defender against pathogens and other external threats.
Its outermost layer is maintained through a remarkable transformation in which skin cells swiftly convert into squames flat, dead cells that provide a tight seal between the living portion of the skin and the world outside.
Throughout our lifetime, squames are continually being shed from the skin surface and replaced by inner cells moving outward,” says Elaine Fuchs, Rockefeller’s Rebecca C. Lancefield Professor, whose lab recently shed new light onto this process.
The skin’s epidermis consists of an inner layer of stem cells that periodically stop dividing and move outward, toward the body surface.
As the cells transit through subsequent layers, they face the increasingly harsh extremes of our environment, like variations in temperature.
This phenomenon, called phase separation, occurs when liquids with mismatched properties come together: The oil prefers to be in the company of other oil, so it separates from the water-based vinegar. The mechanism that allows skin cells to sense.
Quiroz and his colleagues suspected that in skin cells, the dark protein deposits observed, known as keratohyalin granules, form through phase separation and carry molecular messages that, when released, prompt the cells to quickly flatten and die.
To test this idea directly in skin, Quiroz and his colleagues developed a technique to visualize phase separation dynamics without disrupting a cell’s normal processes.
They created mice with a phase separation sensor, a biomolecule that emits green light under the microscope when keratohyalin granules form, and then dissipates when the granules disassemble.
With this method, the researchers were able to show that a protein called filaggrin, which is known to be mutated in some skin conditions, plays a key role in granule formation.
If filaggrin is not functioning properly, phase separation fails to occur, skin lacks keratohyalin granules, and the cells can no longer transform in response to environmental triggers,” says Quiroz.
The findings also shed light on the underlying causes of skin conditions linked to mutations in filaggrin.
For example, when Quiroz engineered filaggrin proteins mimicking mutations associated with atopic dermatitis, skin cells could no longer form normal granules.
We suspect that this lack of phase separation contributes to defects in building the skin barrier, resulting in the inflamed, cracked skin that is seen in these conditions, he says. Fuchs adds that the work might open up entirely new avenues for developing treatments for this and other filaggrin-linked skin diseases.