Imaging cells on two-dimensional substrates allows for detailed characterization of protein organization at high resolution as well as cell response to alterations in biochemistry, mechanical properties, and topological features at the nanoscale; unfortunately, the physiological relevance of such approaches is unclear. In contrast, our approach begins with observation of cells in physiologically relevant environments and then aims to recapitulate behaviors seen in this context in environments that allow for control and imaging at the micro- and nano-scale. For the study of cancer cell invasion, we characterize cell invasive phenotype in three-dimensional tumor approximations (i.e. spheroids) embedded in three-dimensional tissue approximations (collagen-based gels). Studying a variety of aggressive breast cancer cell lines and patient-derived samples, we identified an unusual invasive phenotype associated with round cells demonstrating blebs as their primary protrusion type. Imaging such blebs revealed clusters of β1 integrins, molecules that span the membrane and – when coupled with appropriate integrin sub-units – allow force generation on extracellular matrix proteins and mechano-transduction, at the bleb necks. Here, we characterize aspects of bleb morphology and dynamics and bleb association with active and inactive forms of β1 integrin in a cell line that uses blebs as its primary invasive protrusion and a cell line that does not.  We show that the cell line that uses bleb-adherent migration in a constitutive manner is particularly efficient in its use of its integrins; moreover, we demonstrate how relatively low resolution initial experiments can provoke physiologically relevant behaviors that can be recapitulated and interrogated in simpler, controllable two-dimensional environments where imaging with sub-diffraction resolution is facile.<br/>

Imaging single spheroids, cells, blebs, and integrins: Towards a mechanistic understanding of a novel migratory mode

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.