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Mechanobiology of Disease
Wednesday Speaker Abstracts
20
Mechanobiology of Collective Cell Migration in Health and Disease
Chwee Teck Lim
.
Mechanobiology Institute, National University of Singapore, Singapore.
Cells migrating in sheets or large cohorts tend to behave very differently from cells migrating
individually. Indeed, the distinctive behavior of cells migrating in a collective manner underlies
several important biological processes such as wound closure, maintenance of intestinal
epithelium, developmental processes and even cancer metastasis. Here, we characterized the
kinematic behavior of epithelial cell cohorts migrating under well defined geometrical
constraints. We also study such collective cell migration over areas without cell adherent
proteins to examine the formation of epithelial bridges so as to better wound closure
mechanisms. Our results showed that collective cell migration is not only dependent on extent of
geometrical constraints as well as size of wound, but also that cell-cell adhesion and acto-myosin
contractility can regulate the organization and kinematics of the migrating tissues. We also
investigated the collective migration of benign, non-invasive malignant and highly-invasive
malignant cancer cells. Benign cancer cells are found to exhibit intact cell-cell adhesion and
unidirectional lamellipod formation, and hence produce coordinated migration. On the other
hand, the migration of malignant cancer cells is less coordinated due to the altered or defective
lamellipodial formation and intercellular adhesion.
Cell Mechanotype in Cancer
Amy Rowat
.
University of California, Los Angeles, Los Angeles, CA, USA.
Cell mechanical phenotype, or ‘mechanotype’ can signal a transformation in a cell’s
physiological state, such as in malignant transformation. The current paradigm suggests that
more invasive cells are more deformable. To develop a deeper understanding of cell
mechanotype in cancer progression, we recently invented a mechanotype screening platform that
we call Parallel Microfiltration (PMF). We screened panels of ovarian, breast, and pancreatic
cancer cells, including those treated with small molecules such as chemotherapy agents or
microRNAs. Our results show that we can detect cells based on their status in epithelial-to-
mesenchymal transition and chemoresistance; this is enabling us to screen small molecules to
identify compounds that have anti-cancer effects. Interestingly, we also discovered that more
deformable cancer cells are not always more invasive, suggesting that cell deformability is not
sufficient to predict the invasive capacity of tumor cells.