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Cracking the Skin Barrier: Liquid-Liquid Phase Separation Shines under the Skin.

Alexa Regina Chua Avecilla1, Felipe Garcia Quiroz1

  • 1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.

JID Innovations : Skin Science From Molecules to Population Health
|December 15, 2021
PubMed
Summary

Skin barrier formation involves epidermal keratinocytes transforming into squames, driven by keratohyalin granules. Liquid-liquid phase separation (LLPS) explains how these granules form and disassemble, offering insights into skin barrier disorders.

Keywords:
3D, three-dimensionalAD, atopic dermatitisCE, cornified envelopeEDC, epidermal differentiation complexER, endoplasmic reticulumIDP, intrinsically-disordered proteinKC, keratinocyteKG, keratohyalin granuleLCST, lower critical solution temperatureLLPS, liquid-liquid phase separationPTM, post-translational modificationTG, trichohyalin granuleUCST, upper critical solution temperature

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Area of Science:

  • Biophysics
  • Cell Biology
  • Dermatology

Background:

  • Epidermal keratinocytes (KCs) differentiate into enucleated squames, forming the skin barrier.
  • Keratohyalin granules (KGs) within KCs are crucial for this transformation but their function is poorly understood.
  • Defects in KGs are associated with skin barrier dysfunction and disorders.

Purpose of the Study:

  • To review the role of liquid-liquid phase separation (LLPS) in skin barrier formation.
  • To integrate concepts from LLPS and epidermal biology.
  • To highlight LLPS as a novel mechanism for understanding and treating skin barrier disorders.

Main Methods:

  • Literature review integrating biophysics, LLPS, and epidermal biology.
  • Analysis of current research on KGs and squame formation.
  • Discussion of LLPS dynamics in stratifying epithelia.

Main Results:

  • Keratohyalin granules (KGs) are identified as liquid-like membraneless organelles.
  • Liquid-liquid phase separation (LLPS) drives the assembly and pH-triggered disassembly of KGs.
  • LLPS dynamics are environmentally sensitive and crucial for squame formation.

Conclusions:

  • LLPS provides a biophysical framework for understanding skin barrier formation.
  • Targeting LLPS offers new therapeutic strategies for skin barrier disorders.
  • The skin is an excellent model for studying LLPS in tissue biology.