title: Stem cell differentiation increases membrane-actin adhesion regulating cell blebability, migration and mechanics.
abstract: This study examines how differentiation of human mesenchymal stem cells regulates the interaction between the cell membrane and the actin cortex controlling cell behavior. Micropipette aspiration was used to measure the pressure required for membrane-cortex detachment which increased from 0.15 kPa in stem cells to 0.71 kPa following chondrogenic differentiation. This effect was associated with reduced susceptibility to mechanical and osmotic bleb formation, reduced migration and an increase in cell modulus. Theoretical modelling of bleb formation demonstrated that the increased stiffness of differentiated cells was due to the increased membrane-cortex adhesion. Differentiated cells exhibited greater F-actin density and slower actin remodelling. Differentiated cells also expressed greater levels of the membrane-cortex ezrin, radixin, moeisin (ERM) linker proteins which was responsible for the reduced blebability, as confirmed by transfection of stem cells with dominant active ezrin-T567D-GFP. This study demonstrates that stem cells have an inherently weak membrane-cortex adhesion which increases blebability thereby regulating cell migration and stiffness.
authors.affiliation: Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Mile End Rd, London, E1 4NS, United Kingdom.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sliogeryte
authors.affiliation: Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Mile End Rd, London, E1 4NS, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Thorpe
authors.affiliation: Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Mile End Rd, London, E1 4NS, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Lee
authors.affiliation: Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Mile End Rd, London, E1 4NS, United Kingdom.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Botto
authors.affiliation: Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Mile End Rd, London, E1 4NS, United Kingdom.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Knight
mesh_terms: D000199:Actins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology*; D000099149:Ezrin
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D000099149:Ezrin; C071776:radixin