Individual mouse mitotic chromosomes exhibit cell type-specific differences in biomechanical properties

Brown, K. E.; Patra, S.; Dimond, A.; Ray, K. K.; Cheriyamkunnel, S.; Patel, B.; Gim, D. H.; Whilding, C.; Llobet Ayala, M.; Kilic, M. E.; Rueda, D. S.; Fisher, A. G.

doi:10.64898/2026.09.07.749823

bioRxiv · 10.64898/2026.09.07.749823

Individual mouse mitotic chromosomes exhibit cell type-specific differences in biomechanical properties

Brown, K. E.·Patra, S.·Dimond, A.·Ray, K. K.·Cheriyamkunnel, S.·Patel, B.·Gim, D. H.·Whilding, C.·Llobet Ayala, M.·Kilic, M. E.·Rueda, D. S.·Fisher, A. G.

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Abstract

Cyclic episodes of chromosome compaction and de-condensation are features of eukaryotic cell division that aid mitotic segregation and help prevent aneuploidy. While biophysical data on mitotic chromosome structure has been previously obtained, heterogeneity within samples can confound analyses and precludes direct like-for-like comparisons. To circumvent this, we employed advanced flow cytometry to purify specific metaphase chromosomes with biotinylated telomeres from stably engineered mouse cells. We show that ESC-derived metaphase chromosomes 3 and 19 display distinct properties but share a conserved force-dependent mechanical response. In contrast, chromosome equivalents isolated from NSCs and preB cells show markedly different force-dependent responses, reflecting progressive differentiation stages. Covalent crosslinking of ESC-derived chromosomes alters biomechanical properties to mimic equivalents from more differentiated cells. Collectively, these results highlight the need to isolate specific, homogeneous metaphase chromosome samples to accurately decipher their complex behaviours.

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Brown, K. E., Patra, S., Dimond, A., Ray, K. K., Cheriyamkunnel, S., Patel, B., Gim, D. H., Whilding, C., Llobet Ayala, M., Kilic, M. E., Rueda, D. S., Fisher, A. G.. 2026-09-10. Individual mouse mitotic chromosomes exhibit cell type-specific differences in biomechanical properties. https://doi.org/10.64898/2026.09.07.749823

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