Nuclear lamina strain states revealed by intermolecular force biosensor

Brooke E. Danielsson, Bobin George Abraham, Elina Mäntylä, Jolene I. Cabe, Carl R. Mayer, Anna Rekonen, Frans Ek, Daniel E. Conway () and Teemu O. Ihalainen ()
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Brooke E. Danielsson: Virginia Commonwealth University
Bobin George Abraham: Tampere University
Elina Mäntylä: Tampere University
Jolene I. Cabe: Virginia Commonwealth University
Carl R. Mayer: Virginia Commonwealth University
Anna Rekonen: Tampere University
Frans Ek: Tampere University
Daniel E. Conway: The Ohio State University
Teemu O. Ihalainen: Tampere University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Nuclear lamins have been considered an important structural element of the nucleus. The nuclear lamina is thought both to shield DNA from excessive mechanical forces and to transmit mechanical forces onto the DNA. However, to date there is not yet a technical approach to directly measure mechanical forces on nuclear lamins at the protein level. To overcome this limitation, we developed a nanobody-based intermolecular tension FRET biosensor capable of measuring the mechanical strain of lamin filaments. Using this sensor, we were able to show that the nuclear lamina is subjected to significant force. These forces are dependent on nuclear volume, actomyosin contractility, functional LINC complex, chromatin condensation state, cell cycle, and EMT. Interestingly, large forces were also present on nucleoplasmic lamins, indicating that these lamins may also have an important mechanical role in the nucleus. Overall, we demonstrate that the nanobody-based approach allows construction of biosensors for complex protein structures for mechanobiology studies.

Date: 2023
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DOI: 10.1038/s41467-023-39563-6

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