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Biology subjects

Bell, G. R.

Publications and source records attributed to Bell, G. R..

2 recordsLinked to original sources

Open-source cell culture automation system with integrated cell counting for passaging microplate cultures

Tissue culture in 96-well microplates is conventionally a tedious, highly manual process sensitive to individual technique and experimenter error. Here, we describe the Automated Cell Culture Splitter (ACCS), a system for passaging plates of adherent or suspension cells, for routine culture maintenance or specialized applications such as seeding plates for microscopy. The system is built around the Opentrons OT-2 liquid handling robot and incorporates a novel on-deck imaging-based cell counter which allows it to compensate for density disparities across a source plate and control the number of cells seeded on a per-well basis. We find this solution can cut hands-on time by 61% and the results compare favorably to our existing manual cell culture processes in terms of both seeding density precision and bio-logical outcomes, achieving a control of seeding density with a well-to-well coefficient of variation (CV) under 11%. The system is designed to be adaptable and an accessible entry point into automation for high-throughput cell culture; to that end, all of the source code and hardware designs are released under open source licenses.

bioengineering↗

Wnt/PCP signaling mediates breast cancer metastasis by promoting pro-invasive protrusion formation in collectively motile leader cells

As evidence supporting essential roles for collective cell migration in carcinoma metastasis continues to accumulate, a better understanding of the underlying cellular and molecular mechanisms will be critical to translating these findings to the treatment of advanced cancers. Here we report that Wnt/PCP, a non-canonical Wnt signaling pathway, mediates breast cancer collective migration and metastasis. We observe that mammary gland-specific knockout of Vangl2, a tetraspanin-like scaffolding protein required for Wnt5a-induced signaling and motility in cultured breast cancer cell lines, results in a striking decrease in metastatic efficiency but not primary tumor growth in the MMTV-NDL transgenic mouse model of HER2-positive breast cancer. We also observe that expression levels of core Wnt/PCP components Wnt5a, Vangl1 and Vangl2 are selectively elevated in K14-positive leader cells relative to follower cells within a collectively migrating cohort, and that Vangl2 expression selectively promotes RhoA activation in leading edge cells. Moreover, Vangl expression drives collective migration in three-dimensional ex vivo tumor organoids, and Vangl protein specifically accumulates within pro-migratory filamentous actin-rich protrusions of leader cells. Together, our observations point to a model whereby Wnt/PCP upregulation facilitates breast tumor collective cell motility by selectively augmenting the formation pro-migratory protrusions within leader cells.

cancer biology↗