The deformability of circulating leukocytes plays an important role in the physiopathology of several diseases like sepsis or acute respiratory distress syndrome (ARDS). We present here a microfluidic method for the passive testing, sorting and separating of non-adherent cell populations by deformability. It consists of microfluidic sieves in series with pore sizes decreasing from the upstream to the downstream. The method capabilities are demonstrated with monocytic cell lines (THP-1) treated by Jasplakinolide (a stabilizer of polymerized actin), LatrunculinA (an inhibitor of actin polymerization), and with the plasma of patients suffering from ARDS. Simple sample injection with standard syringes and pumps makes the method readily adapted for experimentation in hospitals.
Epidermal Growth Factor Receptor (EGFR) is an important target of anticancer therapy. Nowadays, the search for new molecules inhibiting this receptor is turning toward natural substances. One of the most promising natural compounds that have shown an anti-EGFR activity is curcumin, a polyphenol found in turmeric. Its effect on the receptor kinase activity and on the receptor autophosphorylation has been already described, but the mechanism of how curcumin interacts with EGFR is not fully elucidated. We demonstrate that the mode of action of curcumin is dual. This polyphenol is able to inhibit directly but partially the enzymatic activity of the EGFR intracellular domain. The present work shows that curcumin also influences the cell membrane environment of EGFR. Using biomimetic membrane models, we show that curcumin insertion into the lipid bilayer leads to its rigidification. Single particle tracking analyses performed in the membrane of A431 cancer cells confirmed that this effect of curcumin on the membrane slows down the receptor diffusion. This is likely to affect the receptor dimerization and, in turn, its activation.
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