Nuclear mechanics and YAP mechanotransduction in health and disease

Datum

01.10.2026

Zeit

11:00 - 12:00

Sprecher

Allen Ehrlicher

Zugehörigkeit

Department of Bioengineering, McGill University, Canada

Serie

MPI-CBG Thursday Seminar

Sprache

en

Hauptthema

Biologie

Host

Alexander von Appen

Beschreibung

The mechanical stiffness of the nucleus regulates its deformation under force, making it an emerging central mechanosensor of the cell, which interacts with numerous signaling macromolecules and pathways. In particular, Yes-Associated Protein (YAP), is a key transcription factor in diverse physiology and disease whose activity is in part regulated by nuclear compression. This makes downstream activity of YAP in diverse contexts directly regulated by the forces applied to the nucleus, as well as the nucleus’s mechanical properties. Previous studies have related nuclear mechanics with YAP activity, but we still lack an understanding of what nuclear deformation specifically regulates YAP, and its relationship with mechanical stimuli. In this talk I will discuss some of our ongoing work and recent findings related to YAP mechanosensing in the nucleus. Our lab has shown that nuclear compression from diverse sources of substrate stiffness mediated contractile force to external osmotic pressure reveal an identical scaling of YAP activity as a function of nuclear volume. I will discuss how examining the details of nuclear deformation in mesenchymal stem cells (MSCs), we find that specifically nuclear curvature is a clear predictor for YAP mechanosensing in the nucleus. By controlling the nuclear curvature, we are able to precisely direct the differentiation lineage of MSCs in culture, with numerous potential therapeutic applications. Beyond differentiation, we have also revealed how nuclear deformation mediated YAP activity regulates cellular senescence. Examining Hutchinson Gilford Progeria Syndrome (HGPS) cells with healthy wild type fibroblasts, we find that HGPS nuclei are stiffer and wrinkled due to the nucleoplasmic spoke-like structure of lamin A/C in HGPS nuclei. We find that increased nuclear stiffness is correlated with reduced YAP activity, which in turn promotes cellular aging as assessed by biomarkers. Directly mechanically compressing stiff cells lead to a dramatic increase in YAP activity and a reduction in cellular aging. These studies of nuclear mechanics reveal its role in YAP mechanotransduction with broad impact across diverse cell functions and pathology.

Letztmalig verändert: 24.08.2026, 07:35:31