The development of materials that selectively mediate the rolling of
cancer cells is important for the high-throughput enrichment of high-speed
cancer cells. Here we constructed a dense and stretched low molecular weight
hyaluronic acid (HA9.6k)-modified surface to selectively promote the rolling of CD44-high
cancer cells. The HA surface (
calcium ion-regulated HA9.6k surface, Ca-rHA) was fabricated via a
calcium ion-regulated method, where
calcium ion incorporation induced the shrink of HA9.6k chains to achieve the highest reported grafting density of about 2.73 ± 0.20 × 104 HA chains μm-2. Upon the removal of
calcium ions, the dense HA9.6k chains switched to a highly stretched conformation. The high density and flexibility of Ca-rHA bearing abundant binding sites enhanced the rolling of CD44-high
cancer cells and reduced the velocity of cells from 1389 µm s-1 to 99 µm s-1 (7%), comparable to that of the physiological rolling event and outperforming traditional grafting-to HA and
E-selectin, without causing phenotypic changes. When processing complex samples under high-speed flow, Ca-rHA selectively mediated the rolling of
cancer cells and enriched their ratio to peripheral blood mononuclear cells from 1:1 to 15:1. As the only reported artificial
biomaterial capable of selectively mediating the rolling of
cancer cells under a physiological high-speed flow, Ca-rHA holds promise in enriching intact cells for downstream analysis in the clinics by encouraging the surface-cell contacts. STATEMENT OF SIGNIFICANCE: The development of materials that selectively mediate the rolling of
cancer cells is important for the high-throughput enrichment of
cancer cells rolling under high-speed flow, yet is less reported. To selectively promote the rolling of cancer stem cell marker CD44-high
cancer cells, a surface with dense and stretched low molecular weight
hyaluronic acid (HA9.6k) was constructed. With Ca2+ regulation, HA9.6k chains shrank to achieve the highest reported grafting density of 2.73 ± 0.20 × 104 chains μm-2 and further switched to a highly stretched conformation after the removal of Ca2+
ions. As the only reported artificial
biomaterial capable of selectively mediating the rolling of
cancer cells under a physiological high-speed flow, this Ca2+-regulated HA9.6k surface holds promise in enriching intact cells for downstream analysis in the clinics.