Using the procedure outlined in the Methods section, we reduced λ max from 0.95 to 0.80, corresponding to a decrease in the required lincs order from 72 to 16. Even though the topology optimization described above efficiently reduced the required lincs order, large distortions of the geometry of the original model can cause other instabilities. In the case of cholesterol, further reduction in lincs order was not possible, because the resulting topologies had massive beads that were too close. Due to the proximity of these massive beads, the integration of the equations of motion produced overly large deviations from the prescribed values leading to a different kind of LINCS instability.