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  Integrin αIIbβ3 activation and clustering in minimal synthetic cells

Benk, L. T., Benk, A. S., Lira, R. d., Cavalcanti-Adam, E. A., Dimova, R., Lipowsky, R., et al. (2022). Integrin αIIbβ3 activation and clustering in minimal synthetic cells. Advanced nanoBiomed research, 2(4): 2100094. doi:10.1002/anbr.202100094.

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 Creators:
Benk, Lucia T., Author
Benk, Amelie S., Author
Lira, Rafael de1, Author              
Cavalcanti-Adam, Elisabetta Ada, Author
Dimova, Rumiana1, Author              
Lipowsky, Reinhard2, Author              
Geiger, Benjamin, Author
Spatz, Joachim P., Author
Affiliations:
1Rumiana Dimova, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863328              
2Reinhard Lipowsky, Theorie & Bio-Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863327              

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Free keywords: cell adhesion; focal adhesion; integrin; integrin clustering; synthetic cell
 Abstract: Platelet adhesion and activation are mediated by integrin αIIbβ3 clustering, which is crucial for the hemostatic function of platelets. In an activated state, integrins provide the connection between the extracellular matrix and the actin cytoskeleton through a variety of cytoplasmic proteins, such as talin. Here, droplet-based microfluidics is applied to generate cell-sized giant unilamellar vesicles (GUVs) with a defined molecular composition to quantify the adhesion of integrin αIIbβ3-containing protocells in relation to the number of integrin–talin head domain (THD) complexes. Furthermore, it is shown that THD induces integrin clustering in protocells adhering to fibrinogen. The formation of this molecular link, which has, so far, only been observed in vivo, is an essential step in synthetic cell design to recapitulate integrin-mediated bidirectional signaling across the membrane. These results pave the way for further quantitative investigations of protein–protein interactions between integrins and associated proteins and their assembly within such defined, but complex, synthetic cells. An essential future step to mimic the complex interaction between cells and their environment will be to combine synthetic approaches with peptide chemistry to guide the molecular mechanisms involved in integrin binding and activation.

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Language(s): eng - English
 Dates: 2022-02-082022
 Publication Status: Published in print
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 Identifiers: DOI: 10.1002/anbr.202100094
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Title: Advanced nanoBiomed research
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: 2 (4) Sequence Number: 2100094 Start / End Page: - Identifier: ISSN: 2699-9307