Beyond Bistability: A Multistable Cascade Model of Bioelectric Cancer Normalization

Every computational model of bioelectric cancer treats the system as bistable: a healthy attractor near −70 mV and a cancer attractor near −10 mV, separated by a single barrier. This paper argues that the real system is more complex and more therapeutically useful than that. Direct microelectrode measurements of unsynchronized MCF-7 breast cancer cells reveal not two but four discrete membrane potential peaks at −9, −17, −25, and −40 mV (Woodfork, Wonderlin & Strobl, 1995). The standard interpretation attributes these peaks to cell cycle phases. We propose an alternative: these peaks represent four quasi-stable bioelectric states forming a cascade between the cancer and healthy attractors. If correct, this reframes normalization from a single difficult jump across 60 mV to a series of smaller, achievable steps of 8–15 mV each. We present a bistable lattice model (reproducing published critical cloud sizes of 5–8 cells radius) and show that instructor cells increase cloud stability by ≈ 6.3×. We construct a toy multistable effective-current model demonstrating that a four-well voltage landscape is dynamically coherent (Supplementary Fig. S1). We then describe a $600 FACS-sorting experiment that distinguishes our hypothesis from the cell-cycle explanation within two weeks. If the cascade model is correct, partial normalization — moving cells one step rather than all the way — becomes a realistic therapeutic target, achievable with existing FDA-approved drugs at doses far lower than those required for full repolarization.