Oxygen plasma micro-nanostructured PMMA plates and microfluidics for increased adhesion and proliferation of cancer versus normal cells: The role of surface roughness and disorder

Abstract

Abstract Micro-nanostructured surfaces play a key role in the understanding of cell-surface interactions. The aim of this work was to study the effect of oxygen plasma micro-nanostructured commercial PMMA plates on the adhesion, morphology and proliferation of normal skin fibroblasts and A431 skin cancer cells. It was found that the adhesion and proliferation of normal skin fibroblasts was significantly inhibited, while their morphology and focal points formation were seriously impaired on plasma treated surfaces with peak-to-valley height ≥ 5 μm as compared to the untreated ones. On the other hand, the adhesion of cancer cells was 2.5–3 times higher in all rough surfaces as compared to the untreated ones, whereas their proliferation rate was considerably improved on the rough surfaces prepared through plasma treatment for 5 and 10 min. Besides, the morphology of cancer cells was not affected on all the micro-nanostructured surfaces tested. The preference of cancer cells for adhesion and proliferation on highly rough surfaces compared to normal cells was exploited for enrichment of cancer cells in co-cultures with normal ones. Thus, for cancer to normal cell seeding ratios from 1/50 to 1/200, after 3 days of culture, enrichment ratios of about 48.5 ± 1.6 were obtained for the 10-min treated micro-nanostructured surfaces as compared to enrichment ratios of 13.8 ± 0.9 obtained for the untreated surfaces. A detailed Fourier and multifractal analysis shows for the first time that this increased enrichment of cancer cells follows the increased surface disorder of the rough surfaces. Moreover, the enhanced adhesion of cancer cells with respect to normal ones onto plasma micro/nanostructured surfaces was investigated under flow conditions using microchannels with micro-nanostructured bottom. In this case, an enrichment ratio of cancer to normal cells of 1.5 was determined compared to 0.5 obtained for the untreated PMMA after 1-h culture with the surface. These results demonstrate the great potential of plasma micro-nanostructured PMMA plates for enrichment of cancer cells from mixtures with normal ones.