Cellular biomechanics impairment in keratinocytes is associated with a C-terminal truncated desmoplakin: An atomic force microscopy investigation. (March 2018)

• Record Type: Journal Article
• Authors: Puzzi, Luca; Borin, Daniele; Martinelli, Valentina; Mestroni, Luisa; Kelsell, David P.; Sbaizero, Orfeo
• Is Part Of: Micron. Volume 106(2018)
• Page Start: 27
• Page End: 33
• Publication Date: 2018-03
• Subjects: Desmoplakin -- Keratinocytes -- Cellular biomechanics -- Atomic force microscopy -- Desmosome -- Cytoplasmic architecture; Microscopy -- Periodicals; Electron Probe Microanalysis -- Periodicals; Microscopy -- Periodicals; Microscopie -- Périodiques; Microscopy; Periodicals; 502.82
• DOI: 10.1016/j.micron.2017.12.005
• Languages: English
• ISSNs: 0968-4328

Abstract

Highlights: DP mutation alters a wide range of biomechanical parameters in human keratinocytes. DP alteration induces morphological changes of the cell. Viscoelasticity differences highlight possible cytoskeletal structure impairment. Abstract: In a tissue continuously challenged by mechanical stresses, such as the skin or the heart, cells perceive information about their microenvironment through several adhesive protein complexes and activate cell-signaling events to maintain tissue cohesion. Consequently, alteration of cell adhesion components leads to aberrant assembly of the associated cytoplasmic scaffolding and signaling pathways, which may reflect changes to the tissue physiology and mechanical resistance. Desmoplakin is an essential component of the cell–cell junction, anchoring the desmosomal protein complex to the intermediate filaments (IFs). Inherited mutations in desmoplakin are associated with both heart and skin disease (cardiocutaneous syndrome). In this study, we investigated the mechanical properties of human keratinocytes harboring a cardiocutaneous-associated homozygous C-terminal truncation in desmoplakin (JD-1) compared to a control keratinocyte line (K1). Using Single Cell Force Spectroscopy (SCFS) AFM-based measurements, JD-1 keratinocytes displayed an overall alteration in morphology, elasticity, adhesion capabilities and viscoelastic properties, highlighting the profound interconnection between the adhesome pathways and the IF scaffold.