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PreprintCC BYbioRxiv

Nuclear speckles comprise hierarchical nanoscale interaction networks that shape molecular dynamics

1 more authors
  1. 1Univ. Illinois

Abstract

Biomolecular condensates organize essential cellular processes, but how their internal architecture regulates molecular behavior in living cells remains poorly understood. Here, we use MINFLUX nanoscopy for quantitative single-molecule imaging and live-cell tracking to resolve the organization and dynamics of specific macromolecules within nuclear speckles. Rather than behaving as uniform liquid-like compartments, nuclear speckles are hierarchically organized into dynamic nanoscale interaction networks. Proteins and RNAs assemble into molecular clusters that generate transient interaction nanodomains, where individual molecules alternate between diffusion and confinement while exploring higher-order networks. Physiological and genetic perturbations selectively remodel molecular clustering and nanodomain organization, and these changes are not consistently coupled to changes in the abundance of the measured components. Together, these findings reveal a multiscale organization of nuclear speckles in which molecular clustering, transient confinement, and dynamic exchange represent distinct but interconnected features of condensate architecture in living cells.

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BibTeX
@misc{liu2026nuclear,
  title = {{Nuclear speckles comprise hierarchical nanoscale interaction networks that shape molecular dynamics}},
  author = {M. Liu and T. Yao and J. Zahringer and Y. J. Song and Q. Meng and D. Futagi and A. D. Haase and S. DeVries and S. M. Freier and S. G. Prasantth and T. Ha and I. Golding and P. Kannanganattu},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.30.763187},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763187v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Nuclear speckles comprise hierarchical nanoscale interaction networks that shape molecular dynamics
AU  - M. Liu
AU  - T. Yao
AU  - J. Zahringer
AU  - Y. J. Song
AU  - Q. Meng
AU  - D. Futagi
AU  - A. D. Haase
AU  - S. DeVries
AU  - S. M. Freier
AU  - S. G. Prasantth
AU  - T. Ha
AU  - I. Golding
AU  - P. Kannanganattu
PY  - 2026
DA  - 2026/10/30
PB  - bioRxiv
DO  - 10.64898/2026.10.30.763187
UR  - https://www.biorxiv.org/content/10.64898/2026.10.30.763187v1
AB  - Biomolecular condensates organize essential cellular processes, but how their internal architecture regulates molecular behavior in living cells remains poorly understood. Here, we use MINFLUX nanoscopy for quantitative single-molecule imaging and live-cell tracking to resolve the organization and dynamics of specific macromolecules within nuclear speckles. Rather than behaving as uniform liquid-like compartments, nuclear speckles are hierarchically organized into dynamic nanoscale interaction networks. Proteins and RNAs assemble into molecular clusters that generate transient interaction nanodomains, where individual molecules alternate between diffusion and confinement while exploring higher-order networks. Physiological and genetic perturbations selectively remodel molecular clustering and nanodomain organization, and these changes are not consistently coupled to changes in the abundance of the measured components. Together, these findings reveal a multiscale organization of nuclear speckles in which molecular clustering, transient confinement, and dynamic exchange represent distinct but interconnected features of condensate architecture in living cells.
ER  -