@article {69994, title = {A multimodal adaptive optical microscope for in vivo imaging from molecules to organisms}, journal = {bioRxiv}, year = {2025}, month = {2025 Jun 16}, abstract = {

Understanding biological systems requires observing features and processes across vast spatial and temporal scales, spanning nanometers to centimeters and milliseconds to days, often using multiple imaging modalities within complex native microenvironments. Yet, achieving this comprehensive view is challenging because microscopes optimized for specific tasks typically lack versatility due to inherent optical and sample handling trade-offs, and frequently suffer performance degradation from sample-induced optical aberrations in multicellular contexts. Here, we present MOSAIC, a reconfigurable microscope that integrates multiple advanced imaging techniques including light-sheet, label-free, super-resolution, and multi-photon, all equipped with adaptive optics. MOSAIC enables non-invasive imaging of subcellular dynamics in both cultured cells and live multicellular organisms, nanoscale mapping of molecular architectures across millimeter-scale expanded tissues, and structural/functional neural imaging within live mice. MOSAIC facilitates correlative studies across biological scales within the same specimen, providing an integrated platform for broad biological investigation.

Preprint:\ https://www.biorxiv.org/content/early/2025/06/13/2025.06.02.657494

}, doi = {10.1101/2025.06.02.657494}, url = {https://www.biorxiv.org/content/early/2025/06/13/2025.06.02.657494}, author = {Fu, Tian-Ming and Liu, Gaoxiang and Milkie, Daniel E. and Ruan, Xiongtao and G{\"o}rlitz, Frederik and Shi, Yu and Ferro, Valentina and Divekar, Nikita S. and Wang, Wei and York, Harrison M. and Kilic, Velat and Mueller, Matthew and Liang, Yajie and Daugird, Timothy A. and Gacha-Garay, Maria J. and Larkin, Kathryn A. and Adikes, Rebecca C. and Harrison, Nathaniel and Shirazinejad, Cyna and Williams, Samara and Nourse, Jamison L. and Sheu, Shu-Hsien and Gao, Liang and Li, Tongchao and Mondal, Chandrani and Achour, Kemal and Hercule, Wilmene and Stabley, Daniel and Emmerich, Kevin and Dong, Peng and Drubin, David and Liu, Zhe J. and Clapham, David and Mumm, Jeff S. and Koyama, Minoru and Killilea, Alison and Bravo-Cordero, Jose Javier and Keene, C. Dirk and Luo, Liqun and Kirchhausen, Tom and Pathak, Medha M. and Arumugam, Senthil and Nunez, James K. and Gao, Ruixuan and Matus, David Q. and Martin, Benjamin L. and Swinburne, Ian A. and Betzig, Eric and Legant, Wesley R. and Upadhyayula, Srigokul} } @article {69089, title = {Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment.}, journal = {Nat. Commun.}, year = {2024}, month = {2024 May 16}, abstract = {

In the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we present an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrate that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacts nucleosome diffusive properties in a manner that is dependent both on local chromatin density and on relative location within the nucleus. Our results support a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Additionally, they reveal that nuclear heterogeneity arises from both active and passive processes and highlight the need to account for different organizational principles when modeling different chromatin environments.

}, doi = {10.1038/s41467-024-48562-0}, author = {Daugird, Timothy A and Shi, Yu and Holland, Katie L and Rostamian, Hosein and Liu, Zhe and Lavis, Luke D and Rodriguez, Joseph and Strahl, Brian D and Legant, Wesley R} }