Programmable Helical Periodicity in Single‐Component Supramolecular Nanofibers for Pitch‐Regulated Cellular Response

ABSTRACT Supramolecular chiral architectures with tunable helical periodicity are essential for mimicking biological complexity and understanding chiral evolution in nature. However, achieving a continuous range of helical pitches, remains a formidable challenge, as conventional methods typically rely on complex multicomponent systems that suffer from chemical heterogeneity and limited predictability. Here, we report that single‐component camptothecin (CPT) spontaneously assembles into homochiral nanofibers with a widely programmable and predictable helical pitch that can be precisely controlled by adjusting the monomer concentration. Such regulatable helical pitches arise from the planar, rigid π ‐conjugated backbone of CPT, affording precise modulation of intermolecular π – π interactions. We then elucidate a hierarchical assembly mechanism transitioning from microaggregates to twisted helical nanofibers, enabling an intense dissymmetry factor ( g _abs ) of up to 0.12. We demonstrate that this modulable pitch enables a 3.21‐fold regulation of cell adhesion efficiency. Mechanistically, we find that helical periodicity dictates cellular response by modulating stereoselective protein adsorption, which subsequently directs focal adhesion formation and cytoskeletal organization. By providing a single‐component strategy for designing programmable chiral architectures, this work establishes helical periodicity as a fundamental physical cue for regulating cellular responses and offers a robust platform for the development of precision‐engineered bioactive chiral nanostructures.