Biophysical Society Bulletin | February 2022

Publications

Know the Editor Kandice Tanner National Cancer Institute

Editor Biophysical Reports

Kandice Tanner

Editor’s Pick Biophysical Journal SARS-CoV-2 spike binding to ACE2 is stronger and longer ranged due to glycan interaction Yihan Huang, Bradley S. Harris, Shiaki A. Minami, Seongwon Jung, Priya S. Shah, Somen Nandi, Karen A. McDonald, Roland Faller “Glycosylation of the receptor binding domain of the spike protein of SARS-CoV-2 as well as the ACE2 receptor leads to stronger and longer ranged binding interactions between the proteins. Particularly at shorter distances, the interactions are between residues of the proteins themselves, whereas at larger distances these interactions are mediated by the glycans.”

What have you read lately that you found really interesting or stimulating? I have been re-reading Rupert A. Willis ’ The Spread of Tumours in the Human Body , published in the mid-20th century. Based on human autopsies, it provides detailed descriptions of different routes of metastasis and tumor outgrowth for rare and understudied cancers. This information is sometimes dif- ficult to find in one or two collective reviews. It has become a valuable resource for my current thinking on our work, which is focused on why different types of cancer spread to distinct groups of organs. What has been your biggest “aha” moment in science? It is difficult to pinpoint a single moment. Instead, I will elaborate on a conceptual leap that allowed us to make one of the lab’s discoveries. Solid cancers often show preferred restricted sites of colonization; for example, uveal melano- ma preferentially metastasizes to the liver. The mechanisms that drive this non-random targeting are not completely understood, nor can it be predicted in individual patients. We reasoned that organ-specific biophysical cues are important, but combinatorial intravital imaging/mechanical mapping of multiple organs in a mouse remains technically challeng- ing. We hypothesized that zebrafish might be an alternative pre-clinical model. Experiments confirmed that signaling pro- teins that guide metastases are sufficiently conserved such that human tumor cells placed into zebrafish show the same preferred colonization sites as they do in mice. Specifically, human breast cancer cell lines that exclusively colonize brain or bone marrow in mice also home to the same organ analogs in zebrafish. Using this animal model, we investigated the role of biophysical properties on non-random metastasis by using home-built, high-resolution optical tweezers in living animals combined with high-resolution intravital fluores- cence imaging. We discovered that the physical properties of the tissue regulate organ-specific organ colonization in a living animal. This organ selectivity is driven by both vessel topography and cell-type–dependent extravasation in the larval zebrafish. I was extremely excited by this study because we can now adapt imaging-based approaches to perform multiplexed measurements in a living animal to understand how organ-specific tissue microenvironmental cues drive metastasis.

Version of Record Published December 6, 2021 DOI:https:/doi.org/10.1016/j.bpj.2021.12.002

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February 2022

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