Chemical Topology of Membrane Fluxes: From Redundant Transport to Neutralization

Malignant cells maintain growth and therapy resistance by overexpressing nutrient transporters (GLUT1/3, LAT1, ASCT2, MCT1/4) within aberrantly glycosylated membranes. These carriers form a redundant influx–efflux lattice: blockade of one pathway is rapidly bypassed, rendering conventional inhibition ineffective. Here we adapt the principle of topological replica neutralization, developed in condensed- matter physics, to oncology. In topological systems, inversion of polarization generates a replica with opposite Euler class; superposition cancels global invariants and removes protected modes. Inspired by this mechanism, we design a biochemical inverse replica that erases malignant redundancy at its structural origin. The strategy uses a branched polyethylene glycol scaffold bearing sulfonates (Cap-PEG- SO− 3 ). Acting as a molecular cap, it enforces Vmax,i 7 → (1 − θi)Vmax,i across transporter families, collapsing glucose, amino acid, and lactate flux coherently. Scaffold sulfonation was validated by FTIR, NMR, and mass spectrometry, while PEGylation ensures solubility and biocompatibility. Within a spectral–topological model, redundancy is recast as a meronic half-covering (Q = 1 2 ) that resists local perturbations. Global capping drives trivialization e(E ⊕ E∗) = 0, annihilating the invariant that stabilizes robustness. The framework yields testable predictions: a critical occlusion θc induces abrupt collapse of Q while Jtot decreases smoothly; θc scales with efflux capacity; and elasticities follow Eθi [Jtot] ≈ −wi([S]). Thus, malignant resilience is reframed as a geometric obstruction rather than a kinetic surplus. By uniting characteristic-class mathematics with scaffold engineering, this work proposes a translational paradigm: neutralization of pathological transport through inverse replicas, linking topology to metabolic oncology.