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Updated: Apr 15, 2026
A Direct Force Probe for Measuring Mechanical Integration Between the Nucleus and the Cytoskeleton
Published on: July 29, 2018
Mechanical interplay between invadopodia and the nucleus in cultured cancer cells
Or-Yam Revach1, Allon Weiner2, Katya Rechav3
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Abstract:
Invadopodia are actin-rich membrane protrusions through which cells adhere to the extracellular matrix and degrade it. In this study, we explored the mechanical interactions of invadopodia in melanoma cells, using a combination of correlative light and electron microscopy. We show here that the core actin bundle of most invadopodia interacts with integrin-containing matrix adhesions at its basal end, extends through a microtubule-rich cytoplasm, and at its apical end, interacts with the nuclear envelope and indents it. Abolishment of invadopodia by microtubules or src inhibitors leads to the disappearance of these nuclear indentations. Based on the indentation profile and the viscoelastic properties of the nucleus, the force applied by invadopodia is estimated to be in the nanoNewton range. We further show that knockdown of the LINC complex components nesprin 2 or SUN1 leads to a substantial increase in the prominence of the adhesion domains at the opposite end of the invadopodia. We discuss this unexpected, long-range mechanical interplay between the apical and basal domains of invadopodia, and its possible involvement in the penetration of invadopodia into the matrix.
Insights
Invadopodia mechanically interact with the cell nucleus, indenting it with nanoNewton forces. This interaction is linked to cell adhesion and matrix degradation, potentially influencing melanoma cell invasion.
Area of Science:
- Cell Biology
- Biophysics
- Cancer Research
Background:
- Invadopodia are crucial for cell adhesion and extracellular matrix degradation.
- Their mechanical role, particularly in cancer invasion, is not fully understood.
Purpose of the Study:
- To investigate the mechanical interactions of invadopodia in melanoma cells.
- To explore the relationship between invadopodia, the nucleus, and cell adhesion.
Main Methods:
- Correlative light and electron microscopy.
- Inhibitor treatments (microtubules, src inhibitors).
- Knockdown of LINC complex components (nesprin 2, SUN1).
Main Results:
- Invadopodia's actin core interacts with matrix adhesions and indents the nuclear envelope.
- Disrupting invadopodia eliminates nuclear indentations, suggesting forces in the nanoNewton range.
- LINC complex disruption enhances invadopodia adhesion domains, indicating long-range mechanical interplay.
Conclusions:
- Invadopodia exert significant mechanical force on the nucleus.
- A long-range mechanical interplay exists between invadopodia's apical and basal domains.
- This interplay may be critical for invadopodia-mediated matrix penetration and cancer cell invasion.
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