Patching of Lipid Rafts by Molecular Self-Assembled Nanofibrils Suppresses Cancer Cell Migration

Summary Cells modify the migration mechanism in response to their surroundings, which sets the challenge for cancer therapy targeting metastasis through signaling pathways. To cope with the diversity and complexity of molecular self-assembled nanofibrils, we have developed a mechanical approach that captures membrane dynamicity to suppress cancer cell migration and invasion. We designed and synthesized a ruthenium (Ru)-complex-based peptidic molecule that selectively initiates self-assembly into extracellular nanofibrils on lipid rafts of cervical cancer cells by reacting with glycosylphosphatidylinositol-anchored placental alkaline phosphatase (GPI-anchored PLAP). The growing nanofibrils glue the lipid rafts and chain them into large clusters, leading to reinforced focal adhesion suppressing cell migration. The molecular self-assembly constantly exerts mechanical stimuli to raft-associated protein receptors, provoking opposing cell migration against focal adhesion with enhanced motility. The contradictory motions generate a mechanical force transferred through the actin cytoskeleton. When the force increases, the restricted cervical cancer cell is ruptured.