Looking forward, there’s still lots of interesting things to do! How is #chromatin rearranged in stem cells during this process? Can we scale up confinement ‘production’ of MSCs for #tissue #engineering applications? Stay tuned for exciting new work from the Confinement Mechanobiology Lab! (8/8)

We got some help from Brian Burke & @ylleecellbio.bsky.social with a DN-KASH #nesprin construct, allowing us to sever the cytoskeleton from the LINC. Since these cells become osteogenic like WT MSCs, nuclear deformation is sufficient for confinement-induced #differentiation. (7/n)

As the #nucleus is heavily deformed inside this confinement, we asked what was more important for this #differentiation response- A) active force applied on the nuclear envelope or B) simple deformation of the nucleus itself? (6/n)

We also found that when MSCs migrate through tight channels, they become more #osteogenic. One thing we love about microchannels: here, the only way those cells could have gotten to the right side is by confined migration, so we know their #confinement history. (5/n)

One of the first things we noticed was that the cell and nuclear morphology of #MSCs changes as a function of the #confinement they have migrated through, and that this change in morphology persists even after they’ve exited into a 2D unconfined microenvironment. (4/n)

Gao Xu was the first PhD student to join my group when I started at @mbisg.bsky.social‬, and he was excited to dive into this question! (3/n)

The seeds of this work started back in my postdoc- I spent a lot of time watching cancer cells migrate through tight spaces, and wondered how these spaces would affect adult stem cells, given their functional (and #mechanosensitive) output of differentiation (2/n)