All Publications


  • Rapid assessment of changes in phage bioactivity using dynamic light scattering. PNAS nexus Dharmaraj, T., Kratochvil, M. J., Pourtois, J. D., Chen, Q., Hajfathalian, M., Hargil, A., Lin, Y. H., Evans, Z., Oromí-Bosch, A., Berry, J. D., McBride, R., Haddock, N. L., Holman, D. R., van Belleghem, J. D., Chang, T. H., Barr, J. J., Lavigne, R., Heilshorn, S. C., Blankenberg, F. G., Bollyky, P. L. 2023; 2 (12): pgad406

    Abstract

    Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-y-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web application (Phage-Estimator of Lytic Function) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and nondestructive tool for quality control of phage preparations in academic and commercial settings.

    View details for DOI 10.1093/pnasnexus/pgad406

    View details for PubMedID 38111822

    View details for PubMedCentralID PMC10726995

  • Cellular Pushing Forces during Mitosis Drive Mitotic Elongation in Collagen Gels. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Nam, S., Lin, Y. H., Kim, T., Chaudhuri, O. 2021; 8 (4): 2000403

    Abstract

    Cell elongation along the division axis, or mitotic elongation, mediates proper segregation of chromosomes and other intracellular materials, and is required for completion of cell division. In three-dimensionally confining extracellular matrices, such as dense collagen gels, dividing cells must generate space to allow mitotic elongation to occur. In principle, cells can generate space for mitotic elongation during cell spreading, prior to mitosis, or via extracellular force generation or matrix degradation during mitosis. However, the processes by which cells drive mitotic elongation in collagen-rich extracellular matrices remains unclear. Here, it is shown that single cancer cells generate substantial pushing forces on the surrounding collagen extracellular matrix to drive cell division in confining collagen gels and allow mitotic elongation to proceed. Neither cell spreading, prior to mitosis, nor matrix degradation, during spreading or mitotic elongation, are found to be required for mitotic elongation. Mechanistically, laser ablation studies, pharmacological inhibition studies, and computational modeling establish that pushing forces generated during mitosis in collagen gels arise from a combination of interpolar spindle elongation and cytokinetic ring contraction. These results reveal a fundamental mechanism mediating cell division in confining extracellular matrices, providing insight into how tumor cells are able to proliferate in dense collagen-rich tissues.

    View details for DOI 10.1002/advs.202000403

    View details for PubMedID 33643782

    View details for PubMedCentralID PMC7887597

  • Cellular Pushing Forces during Mitosis Drive Mitotic Elongation in Collagen Gels ADVANCED SCIENCE Nam, S., Lin, Y., Kim, T., Chaudhuri, O. 2021