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Patterning the Geometry of Human Embryonic Stem Cell Colonies on Compliant Substrates to Control Tissue-Level Mechanics
Published on: September 28, 2019
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Cell Surface Mechanics Gate Embryonic Stem Cell Differentiation
Martin Bergert1, Sergio Lembo1, Sumana Sharma2
1Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Cell Stem Cell
|November 18, 2020
Summary
Cell surface mechanics regulate stem cell differentiation. Decreased membrane-to-cortex attachment allows mouse embryonic stem cells to exit naive pluripotency, a process reversible by mechanical tethering.
Area of Science:
- Cell Biology
- Biophysics
- Developmental Biology
Background:
- Cell differentiation involves shape changes requiring altered surface mechanics.
- The role of cell surface mechanics in controlling differentiation remains largely unknown.
Purpose of the Study:
- To investigate whether cell surface mechanics, specifically membrane-cortex attachment, regulate the exit from naive pluripotency in mouse embryonic stem cells.
Main Methods:
- Measurement of membrane tension during early stem cell differentiation.
- Mechanical manipulation of plasma membrane-to-cortex attachment via Ezrin activity modulation and synthetic linkers.
Main Results:
- Naive stem cells decrease plasma membrane-to-cortex attachment during the transition to a primed state.
- Preventing this detachment by mechanical tethering forces stem cells to maintain naive pluripotency.
Conclusions:
- Reduced membrane-to-cortex attachment is a novel cell-intrinsic mechanism essential for exiting pluripotency.
- Membrane mechanics act as a critical gatekeeper for stem cell differentiation.

