Measuring Cell Squishiness Could Aid Cancer Drug Discovery

    In this modern genomic age, it would almost seem archaic to devise a screening method that relies on changes in cellular architecture that occur when a cell turns cancerous and not on molecular mutations. However, sometimes the simplest and most direct solutions provide the best results.

    Since scientists previously established that many types of cancer cells are spongier and more pliable than normal, healthy cells, researchers at UCLA have developed a screening method that utilizes this information to classify different types of cancer cells and that could ultimately lead to better treatments for cancer, diabetes, malaria, and a host of other diseases.

    “We want to screen cells based on their squishiness or stiffness,” explained senior author Amy Rowat, Ph.D., assistant professor and a member of UCLA’s Jonsson Comprehensive Cancer Center. “We created a technology to probe the deformability of hundreds of cell samples at the same time, so we can identify compounds that make the cells stiffer. Our hope is that we can identify new compounds that can help to prevent the spread of cancer.”

    Dr. Rowat and her team devised a method that begins by placing a mixture of cells and liquid on a porous membrane and applying air pressure to force the mixture down through tiny pores that have a smaller circumference than the cells. Stiffer cells block the pores so that not much liquid can filter through—however, for squishier cell types like cancer, more of the cell-and-liquid mixture passes through the membrane. The UCLA team calls their approach parallel microfiltration method, or PMF. This method allows investigators to assay many different small molecules at once by measuring the filtration of fluid into individual compartments.

    The findings from this study were published recently in Scientific Reports through an article entitled “Screening cell mechanotype by parallel microfiltration.”

    Dr. Rowat’s team discovered that drug-resistant human ovarian cancer cells are softer than their drug-sensitive counterparts and that more invasive cancer cells are softer than less-invasive ones.

    “Inducing epithelial-to-mesenchymal transition (EMT) in human ovarian cancer cells by overexpression of key transcription factors (Snail, Slug, Zeb1) or by acquiring drug resistance produces a similar increase in deformability,” the authors stated. “Mechanistically, we show that EMT-mediated changes in epithelial (loss of E-Cadherin) and mesenchymal markers (vimentin induction) correlate with altered mechanotype. Our results demonstrate a method to screen cell mechanotype that has the potential for broader clinical application.”

    In future studies, The UCLA researchers hope to establish whether squishier cancer cells are in fact more harmful than stiffer cancer cells and whether their pliability can be reversed. Dr. Rowat added that “it’s easy to imagine softer cells can spread more easily through the body to invade distant tissues, but this is still a hypothesis.”

    Dr. Rowat and her team were excited by their findings and hope to fine tune their method for expansion into other researcher disciplines. Moreover, parallel microfiltration’s broader applications could include the ability to screen molecules that can alter particular genes and protein levels inside a cell, which could be useful for treating a variety of other diseases.