Nuclear Mechanics and Mechanotransduction in Cellular Systems

The cell nucleus is not merely a repository for genetic material but a dynamic mechanical entity that senses, transmits and responds to forces. Its structural integrity arises from the nuclear envelope—comprising inner and outer membranes—and the underlying lamina, a meshwork of lamin proteins that tether chromatin and connect to cytoskeletal networks via the LINC complex. Mechanical cues from cell–matrix adhesion, shear stress or confinement are conveyed through actomyosin contractility and perinuclear actin structures to the lamina and chromatin, leading to changes in nuclear shape, stiffness and gene expression. Such mechanotransduction underpins processes as diverse as stem cell differentiation, immune cell migration, cancer invasion and tissue development. Disruption of nuclear mechanics is implicated in laminopathies, altered regenerative capacity and genome instability, highlighting the clinical importance of understanding how external and internal forces modulate nuclear architecture and function.

Research from Nature Portfolio

Recent advances have enabled direct quantification of forces on nuclear lamins in living cells. A novel nanobody-based intermolecular tension FRET biosensor revealed that lamin filaments bear substantial mechanical strain that varies with nuclear volume, chromatin condensation, LINC complex integrity and actomyosin activity. This approach uncovered forces not only at the nuclear periphery but also on nucleoplasmic lamins, suggesting a broader mechanical role for the lamin network in genome protection and organisation. In parallel, studies of melanoma cell invasion have shown that the inner nuclear membrane protein LAP1C modulates nuclear adaptability under confinement. By weakening envelope–lamina coupling, high LAP1C expression facilitates nuclear blebbing and passage through tight interstitial spaces, thereby promoting metastatic migration and tissue colonisation.

Nuclear Mechanics and Mechanotransduction in Cellular Systems publication trend

The graph below shows the total number of articles in nuclear mechanics and mechanotransduction in cellular systems across all publications each year (not limited to Nature Index journals).

Technical terms

Nuclear lamina: A filamentous network of lamin proteins underlying the inner nuclear membrane that provides structural support and links to chromatin.

LINC complex: The linker of nucleoskeleton and cytoskeleton, composed of nesprin and SUN proteins, that mechanically couples the nucleus to the cytoskeleton.

Mechanotransduction: The process by which mechanical forces are converted into biochemical signals, influencing cellular behaviour and gene expression.

Actomyosin contractility: Force generation by the interaction of actin filaments and myosin motors, driving cytoskeletal tension.

Chromatin condensation: The organisation of DNA and histones into tightly packed or relaxed states, affecting nuclear stiffness and transcriptional activity.

Nuclear blebbing: Localised protrusions of the nuclear envelope occurring when nucleus–lamina coupling is weakened, facilitating migration through constricted environments.

References

1. Nuclear lamina strain states revealed by intermolecular force biosensor. Nature Communications (2023).
2. LAP1 supports nuclear adaptability during constrained melanoma cell migration and invasion. Nature Cell Biology (2023).
3. Cyclic Stretch Promotes Cellular Reprogramming Process through Cytoskeletal‐Nuclear Mechano‐Coupling and Epigenetic Modification. Advanced Science (2023).
4. The Interaction between Nesprins and Sun Proteins at the Nuclear Envelope Is Critical for Force Transmission between the Nucleus and Cytoskeleton*. Journal of Biological Chemistry (2011).
5. A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration. Biophysical Journal (2016).