Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

34-POS Board 34 Relative Adhesion Profiler System for Biophysical Interrogation of Malignant Breast Cancer Phenotypes Harsha M. Kittur 1 , Andy Tay 1 , Avery Hua 1 , Min Yu 2 , Dino Di Carlo 1,3,4 . 1 UCLA, Los Angeles, CA, USA, 2 University of Southern California, Los Angeles, CA, USA, 3 California NanoSystems Institute, Los Angeles, CA, USA, 4 Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. Breast cancer mortality is linked to metastasis and currently we lack sufficient biomarkers that accurately predict locations of metastases, enabling improved treatment. We aim to complement current genetic biomarkers with physiologically-relevant physical biomarkers associated with cell adhesion and migration. Here, cells are seeded on a PDMS surface patterned with large stripes of eight different extracellular matrix proteins, and are sandwiched from above with another protein-coated surface with the same eight stripes running orthogonally, to interrogate large groups of cells with 64 protein pair combinations. We quantified percent cell transfer to the top surface for each protein pair over five breast cell lines with unique metastatic potential – normal breast cells (hMEC), malignant breast cancer cells (MDA-MB-231) and MDA-MB-231 cells that have tropism to brain, lung, and bone – to generate relative adhesion plots that can distinguish the populations. These heat maps generally reveal transfer of malignant cells toward collagen 1, but also shows transfer away from basement membrane proteins collagen 4 and laminin, regardless of the type of new protein that is introduced. Morphological analyses show that hMEC display epithelial behavior favoring cell-cell contact via amoeboid motions as opposed to adhesion to the new surface. In contrast, MDA-lung cells tend to move with a mesenchymal phenotype as they switch to a new collagen 1 surface. Antibodies to alpha 2 and beta 1, but not with alpha 6 integrins interfere with transfer. The actin cytoskeleton, but not microtubules or myosin II are implicated in the transfer process. Finally, further analyses of select protein pair combinations provide potential to develop protocols that can separate malignant cells from non-cancerous cells, and then further delineate the malignant cells by their tropism to specific secondary sites.

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