Cell Cycle\nModulation through Physical Confinement\nin Micrometer-Thick Hydrogel Sheaths

Recently, surface engineering of the cell membrane with\nbiomaterials\nhas attracted great attention for various biomedical applications.\nIn this study, we investigated the possibility of modulating cell\ncycle progression using alginate and gelatin-based hydrogel sheaths\nwith a thickness of ∼1 μm. The hydrogel sheath was formed\non cell surfaces through cross-linking catalyzed by horseradish peroxidase\nimmobilized on the cell surface. The hydrogel sheath did not decrease\nthe viability (>95% during 2 days of culture) of the human cervical\ncarcinoma cell line (HeLa) expressing the fluorescent ubiquitination-based\ncell cycle indicator 2 (HeLa/Fucci2). Coating the HeLa/Fucci2 cells\nwith the hydrogel sheath resulted in a cell cycle arrest in the G2/M\nphase, which can be caused by the reduced F-actin formation. As a\nresult of this cell cycle arrest, an inhibition of cell growth was\nobserved in the HeLa/Fucci2 cells. Taken together, our results demonstrate\nthat the hydrogel sheath coating on the cell surface is a feasible\napproach to modulating cell cycle progression.