Basement membrane turnover controls cell shape

Area of Science:

• Biophysics
• Cell Biology
• Biomaterials Science

Background:

• Cell shape regulation is crucial for tissue function.
• The basement membrane (BM) is a key regulator of cell shape in epithelia.
• Little is known about how BM mechanical properties influence cell shape.

Purpose of the Study:

• To investigate how basement membrane mechanical properties regulate cell shape.
• To establish a multiscale framework for probing matrix turnover and its function.

Main Methods:

• Mathematical modeling to link BM stress relaxation time to cell shape.
• Molecular dynamics simulations to infer BM stress relaxation from collagen IV molecule lifetime.
• Development of a fluorescent timer reporter to measure collagen IV lifetime in vivo.

Main Results:

• Basement membrane stress relaxation time was identified as a regulator of cell shape.
• Collagen IV molecule lifetime correlates with the stress relaxation time of collagen IV networks.
• Perlecan was found to modify collagen IV lifetime in vivo.

Conclusions:

• A multiscale framework was established to study matrix turnover and its role in cell shape control.
• Basement membrane mechanical properties, specifically stress relaxation time, are critical for regulating cell shape.
• The developed fluorescent timer reporter allows in vivo measurement of matrix component turnover.