Cellular tension encodes local Src-dependent differential β₁ and β₃ integrin mobility.

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Integrins are key transmembrane receptors mediating cell-extracellular matrix interactions and mechanotransduction.
• Integrin dynamics are crucial for cellular responses, but their dependence on local mechanical cues is not fully understood.

Purpose of the Study:

• To investigate how local mechanical tension and cytoskeletal organization influence integrin mobility within single cells.
• To elucidate the specific roles of beta-1 (β1) and beta-3 (β3) integrin subunits in mechanosensing.

Main Methods:

• Utilized micropatterning to apply defined mechanical constraints to single cells.
• Employed temporal image correlation spectroscopy to quantify integrin mobility and residence time.
• Conducted structure-function studies using chimeric integrins and analyzed phosphorylation by Src family kinases.

Main Results:

• High local tension increased the residence time of β3 integrins in adhesion sites, whereas β1 integrin mobility showed a different response.
• The cytoplasmic domain of β3 integrins was identified as critical for sensing local tensional organization.
• Phosphorylation of NPXY domains by Src family kinases regulates β3 integrin mechanosensitivity.

Conclusions:

• Integrin mobility is mechanosensitive, with β3 integrins exhibiting a distinct response to local tension compared to β1 integrins.
• The cytoplasmic tail of β3 integrins plays a critical role in mediating this tension-dependent regulation of integrin dynamics.
• Src family kinase-mediated phosphorylation is a key regulatory mechanism for β3 integrin-based mechanotransduction.