Centre for the Cellular Microenvironment

@theglasgowcemi.bsky.social

We are a Glasgow-based multidisciplinary team of bio- and cell engineers. We focus on understanding the interactions between materials, proteins and cells to gain insight into engineering cell behaviour and translating technologies into better healthcare.

Great work, with involvement of CeMi member @carstenschulte4.bsky.social, providing new insights on what is happening during nuclear mechanotransduction in stem cells:

Carmelo Ferrai@carmeloferrai.bsky.social · 6mo ago

Tread -1- EpiSci - I am very proud to share with you our new study that you can access on @biorxivpreprint.bsky.social (see link below) "The Interaction with Nanotopographical Environment regulates nuclear mechanoresponse in mESCs via Histone Demethylase KDM3A. www.biorxiv.org/content/10.6...

It finally happened. I'm beyond happy to see this work with @carmeloferrai.bsky.social is out now. This collaboration to study the link between mechanotransduction and epigenetic regulation started quite a while ago. It is kind of a miracle that we eventually got to this point against all odds.

Carmelo Ferrai@carmeloferrai.bsky.social · 6mo ago

Tread -1- EpiSci - I am very proud to share with you our new study that you can access on @biorxivpreprint.bsky.social (see link below) "The Interaction with Nanotopographical Environment regulates nuclear mechanoresponse in mESCs via Histone Demethylase KDM3A. www.biorxiv.org/content/10.6...

A little more than a year that @carmeloferrai.bsky.social and I published our review "Mechanotransduction in stem cells"🤯! I'm happy that it was received well 😃! Stay tuned, more to come in this direction in a not too far future😎.

Carmelo Ferrai@carmeloferrai.bsky.social · 2y ago

EpiSci - Hi there! Our review “Mechanotransduction in stem cells” is finally published. With @carstenschulte4.bsky.social we provided a comprehensive picture, that aims to cover the whole mechanotransductive pathway from the cell microenvironment to the nucleus. 1/3 pubmed.ncbi.nlm.nih.gov/38729084/

A chat with Prof. Viola Vogel (Department of Health Sciences and Technology, ETH Zürich), whose pioneering work in mechanobiology has been key to show that proteins act as mechano-chemical switches which can be exploited in the treatment of various diseases. podcasts.apple.com/gb/podcast/m...

Making progress in mechanobiology (with Prof Viola Vogel)

Podcast Episode · The CeMi Podcast · 20/03/2025 · 23m

podcasts.apple.com

Consistently, some years later (2019), Changede et al. (Sheetz group) showed the existence of integrin nanoclusters bridges build up by activated, but unliganded, integrins. The binding to the thin matrix fibres was mediated by integrins in this case, but it's intriguing to think that this 1/2

This ligand binding-independent integrin signalling was driven by membrane tension. Indeed, the induction of this non-canonical integrin signalling was not restricted to uPAR/vitronectin interaction. This work introduced the cell membrane as a critical component of the molecular clutch.

Figure 7. uPAR/VN signalling requires cell adhesion, ECM rigidity and membrane tension
A.
uPAR‐induced signalling requires cell attachment. Cells expressing uPART54A were seeded on an anti‐uPAR monoclonal antibody (α‐uPAR) or on VNRAD (with uPA) for 30 min. For ‘off‐plate’ experiments, cells were incubated in suspension with these components. Phosphorylation of p130Cas SD is shown in percentage of the positive control, that is the same cells seeded on VNRAD in the presence of uPA (n ≥ 3, mean ± SEM). Representative blots are shown.
B.
uPAR‐induced cell spreading requires adhesion to a rigid matrix. Representative images of 293 cells expressing uPART54A plated in presence of uPA on hydrogels coated with VNRAD at different rigidity (soft: 0.7 kPa, Rigid: 40 kPa) for 30 min. Scale bar: 10 μm.
C.
Effect of plasma membrane relaxation on uPAR or integrin‐induced cell spreading. 293 cells expressing uPART54A were seeded on FN or VNRAD (with uPA) in presence of sucrose (150 mM) or deoxycholate (0.4 mM) for 30 min. Cell‐matrix contact area was quantified. Measurements represent at least 50 cells with indicated geometrical means ± 95% CI, in at least two independent experiments. The grey bars represent the range of cell area of not spread or fully spread uPART54A cells based on 95% CI on poly‐D‐lysine or on VN with uPA, respectively (Fig 2B).
D.
Increased membrane tension induces integrin‐dependent cell spreading. Cells were seeded on PDL for 30 min in presence or absence of 4B4. Where indicated, an equal volume of hypotonic buffer (H2O with 1 mM MgCl2 and 1.2 mM CaCl2) or isotonic (medium) buffer was added to increase plasma membrane tension. Cell‐matrix contact area was assayed and quantified. Measurements represent at least 50 cells with indicated geometrical means ± 95% CI, in at least two independent experiments. Representative DIC images of cells on PDL treated with isotonic or hypotonic medium are shown. Scale bar: 10 μm.

This study assessed the possibility of ligand-independent adhesion signalling by integrins, which was a quite controversial hypothesis at the time (maybe still is). We found that e.g. uPAR-mediated adhesion to vitronectin can induce integrin signalling that does not require integrin ligand binding:

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