Assessing mechanical properties of benign and malignant prostate tissue.

Adhesion strength and contractility enable metastatic cells to become adurotactic

“…While material properties change between tumors (Ahn et al, 2010;Burgstaller et al, 2017;Cox and Erler, 2011;Krupski et al, 2010;Pankova et al, 2019;Paszek et al, 2005;White, 2015;Zhai et al, 2010) and can be affected by cancer treatment (Miller et al, 2018), we found that durotactic behavior and migration speed can be tuned by actomyosin contractility, without any direct tweaks to protein expression levels. This suggests that the differences in migratory behavior are indeed linked directly to cell mechanotype within its niche.…”

“…Additionally, just this difference in max SF force enables the model to correctly predict durotactic differences (Figure 3C) and the accumulation of SA cells on stiffer substrates versus uniform distribution of WA cells across the gradient over 24 h for mammary cells (Figure 3D; Video S7). Importantly, when substrate stiffness is altered to resemble the prostate cancer stiffness gradient (Ahn et al, 2010;Krupski et al, 2010;Zhai et al, 2010), mammary cell parameters (Table S1) cause SA cells to not durotax (Figure S4D). However, when substrate stiffness range is maintained, i.e., 0.35 to 1.8 kPa, but the gradient made more shallow, we do not observe changes in cell accumulation on the stiff region of the substrate for SA cells; i.e., they continue to durotax; for WA cells under the same conditions, they still fail to accumulate (Figure S4E).…”

“…Here, we report that weakly adherent populations of various types of cancers cells are significantly less durotactic than their strongly adherent counterparts, potentially explaining how tumor cells migrate down stiffness gradients. Using the parallel plate flow chamber (PPFC) (Beri et al, 2020), cells are isolated based on adhesion strength and seeded onto photopatterned hydrogels with alternating soft and stiff elasticity profiles that match Young's moduli of softer stromal and stiffer tumor extracellular matrix (ECM) for each type of cancer (Figures 1A and 1B), i.e., 0.3 and 1.5 kPa for mammary (Cox and Erler, 2011;Paszek et al, 2005), 4 and 20 kPa for lung (Burgstaller et al, 2017;Pankova et al, 2019;White, 2015), and 10 and 30 kPa for prostate (Ahn et al, 2010;Krupski et al, 2010;Zhai et al, 2010). When cells were plated on these gradients and observed by time-lapse video microscopy (Videos S1, S2, and S3), we found that strongly adherent (SA) cells on average migrate significantly slower than their weakly adherent (WA) counterparts for mammary, lung, and prostate cancer cell lines (Figure 1C; Figure S1A) on stiff substrates, and slightly slower on softer substrates.…”