Poly(2‐Propyl‐2‐Oxazoline)‐Induced Lipid Nanotube Formation in Phospholipid Multilayers

ABSTRACT Synthetic amphiphilic polymers are promising regulators of biomembrane morphology because of their moderate hydrophobicity and tunable molecular properties, including higher‐order structure, charge, topology, and stimuli responsiveness. However, few studies have demonstrated the direct morphological control of membranes using such polymers, and systematic molecular design strategies remain underdeveloped. In this study, we report that poly(2‐propyl‐2‐oxazoline) (PPOx), a representative amphiphilic polymer, induces the formation of long string‐like structures from multilayered phospholipid films coated on silica particles. Cryo‐electron microscopy suggests that these structures are hollow lipid nanotubes, and fluorescence recovery after photobleaching (FRAP) confirmed the lateral mobility of lipids within the membranes. Furthermore, we developed an image analysis pipeline to quantitatively assess nanotube formation and evaluated the tube‐inducing efficiency of a series of poly(2‐alkyl‐2‐oxazoline) homopolymers with varying side‐chain hydrophobicities.