Imaging and force spectroscopy on desmoglein 1 using atomic force microscopy reveal multivalent Ca2+-dependent, low-affinity trans-interaction

Jens Waschke, Carlos Menendez-Castro, Paola Bruggeman, Rainer Koob, Masayuki Amagai, Hermann J. Gruber, Detlev Drenckhahn, Werner Baumgartner

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Desmoglein 1 is a desmosomal member of the cadherin family expressed in stratified epithelia. Desmoglein 1 is the target adhesion molecule of severe blistering skin diseases such as pemphigus or bullous impetigo. However, despite this enormous pathological relevance, the molecular binding properties of desmoglein 1 are largely unknown. Using atomic force microscopic imaging, we found that desmoglein 1 molecules displayed Ca2+-dependent conformational changes of the extracellular domains. By single-molecule force-distance cycles, we provide evidence that desmoglein 1 undergoes Ca 2+-dependent (K d = 0.8 mm Ca2+) homophilic trans-interaction, which is highly relevant for the contribution of desmoglein 1 homophilic binding to keratinocyte cohesion in distinct epidermal layers. Moreover, while the single-unit unbinding force is comparable to other cadherins (∼40 pN at retrace velocity of 300 nm/s), apparent differences with respect to multivalency of interaction and lifetime of single bonds (0.17 s) were observed. Thus, besides the biophysical characterization of desmoglein 1, a main outcome of the study is that desmoglein 1 differs from other members of the cadherin family in terms of some molecular binding properties.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalJournal of Membrane Biology
Volume216
Issue number2-3
DOIs
Publication statusPublished - 2007 Apr

Fingerprint

Desmoglein 1
Atomic Force Microscopy
Spectrum Analysis
Cadherins
Desmosomal Cadherins
Impetigo
Pemphigus
Keratinocytes
Skin Diseases
Epithelium
Outcome Assessment (Health Care)

Keywords

  • Atomic force microscopy
  • Cadherin
  • Cell adhesion
  • Desmosome
  • Pemphigus

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Cite this

Imaging and force spectroscopy on desmoglein 1 using atomic force microscopy reveal multivalent Ca2+-dependent, low-affinity trans-interaction. / Waschke, Jens; Menendez-Castro, Carlos; Bruggeman, Paola; Koob, Rainer; Amagai, Masayuki; Gruber, Hermann J.; Drenckhahn, Detlev; Baumgartner, Werner.

In: Journal of Membrane Biology, Vol. 216, No. 2-3, 04.2007, p. 83-92.

Research output: Contribution to journalArticle

Waschke, Jens ; Menendez-Castro, Carlos ; Bruggeman, Paola ; Koob, Rainer ; Amagai, Masayuki ; Gruber, Hermann J. ; Drenckhahn, Detlev ; Baumgartner, Werner. / Imaging and force spectroscopy on desmoglein 1 using atomic force microscopy reveal multivalent Ca2+-dependent, low-affinity trans-interaction. In: Journal of Membrane Biology. 2007 ; Vol. 216, No. 2-3. pp. 83-92.
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