Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Wednesday Speaker Abstracts

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.

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