[disclaimer, work for Digital Science, whose parent company owns the parent (or just merged?) company that produces Nature, my own thoughts etc.]

Nature have paid editors who also review articles before they go out for peer review, which means they have fairly obvious costs per article submitted (on top of other things like organising peer review). However, you don't pay to submit, you only pay if you're accepted. Nature accepts, I think, about 5% of the articles submitted to them. That means that for every fixed cost per submission the cost per paper published is 20x higher.