Super-Resolution Imaging Reveals Stretch-Induced Architectural Rearrangement of Desmoplakin in Desmosomes

Area of Science:

• Cell biology
• Biophysics
• Dermatology

Background:

• Desmosomes (DSMs) are crucial intercellular junctions providing mechanical resilience to tissues like the epidermis.
• Desmoplakin (DP) is a key DSM protein anchoring keratins, essential for tissue integrity under mechanical stress.
• DP mutations cause skin fragility disorders, but mechanical force effects on DSM architecture are unclear.

Purpose of the Study:

• To investigate how physiological stretch influences desmoplakin (DP) architecture within desmosomes (DSMs).
• To determine if DP isoforms exhibit differential responses to mechanical strain.
• To elucidate the role of DP in tissue adaptation to biomechanical forces.

Main Methods:

• Normal human epidermal keratinocytes (NHEKs) and DP-knockout keratinocytes expressing DP isoforms were subjected to 13% uniaxial strain for 30 minutes.
• Direct stochastic optical reconstruction microscopy (dSTORM) was employed to visualize DP architecture at 20 nm resolution.
• Comparison of DP structure under static versus stretched conditions across different cell lines.

Main Results:

• Mechanical stretch significantly increased the distance between DP cytoplasmic tails compared to static controls.
• No significant change was observed in the N-terminal head domain of DP under stretch.
• The DP tail domain demonstrated to be the primary site of mechanical adaptation.

Conclusions:

• Physiological stretch alters DP architecture in DSMs, primarily affecting the C-terminal tail domain.
• DP isoforms undergo strain-induced conformational changes, reorganizing DSM architecture in response to stress.
• Understanding DP's biomechanical behavior is vital for insights into dermatological health and disease mechanisms.