Grasping the dynamics of molecular phenomenon appears to be rather challenging for students in the context of life science. To pursue the origin of such difficulties this paper investigates students' (n = 43) meaning making, in interaction with peers and an animation, of the dynamic process of ATP-synthase. To support this inquiry we introduce the CharM-framework (Characteristics of Metaphors), which accounts for students' experiences of metaphors while interacting with external representations (ERs) when trying to make meaning of molecular phenomena. Student-expressed metaphors are outlined and related to the animator's intentions while designing the animation. The analysis shows that some of the used metaphors possess in-built problematic characteristics that could act as potential problems for learning. For example, the metaphors machine and watermill possess problematic characteristics that are a possible reason for students' difficulties with understanding the ATP-synthesis as a reversible and non-deterministic process. Furthermore, we also conclude that students' use of metaphors is highly influenced by the ER, which is designed according to the animator's internal representation of the scientific phenomenon and his intentions. The challenge associated with designing educational representations that sufficiently represent molecular processes is somewhat similar to the challenge student face while linking the characteristics of metaphors to the molecular processes. The CharM-framework can assist in the design process by allowing designers to reflect on how ERs could be interpreted or misinterpreted and also guide teachers' choice of educational representations. (Contains 1 figure, 3 tables, and 4 endnotes.)