Lee Hong-Pyo, Alisafaei Farid, Adebawale Kolade, Chang Julie, Shenoy Vivek B, Chaudhuri Ovijit
Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Sci Adv. 2021 Jan 8;7(2). doi: 10.1126/sciadv.abd4058. Print 2021 Jan.
Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths.
当迁移路径预先存在且具有弹性时，在受限微环境中的细胞迁移受到坚硬细胞核通过孔隙变形能力的限制，但细胞如何产生这些路径仍不清楚。在这里，我们揭示了一种机制，通过该机制细胞核在受限微环境中为间充质干细胞（MSCs）机械地生成迁移路径。MSCs在纳米多孔、受限的粘弹性和塑性水凝胶中能强劲迁移，但在弹性更强的水凝胶中则不能。为了迁移，MSCs首先伸出细的突起，这些突起会随着时间因核活塞作用而变宽，从而在受限基质中开辟出一条迁移路径。理论建模和实验表明，细胞核向突起内推进激活了机械敏感离子通道，导致离子流入，增加了渗透压，该渗透压超过静水压力从而驱动突起扩张。因此，细胞核不是限制迁移，而是通过生成迁移路径为迁移提供动力。
