When studying the molecular aspect of the life sciences, learners must be introduced to somewhat inaccessible phenomena that occur at the sub-micro scale. Despite the difficulties, students need to be familiar with and understand the highly dynamic nature of molecular processes. Thus, external representations1 (ERs) can be considered unavoidable and essential tools for student learning. Besides meeting the challenge of interpreting external representations, learners also encounter a large array of abstract concepts2, which are challenging to understand (Orgill & Bodner, 2004). Both teachers and learners use metaphorical language as a way to relate these abstract phenomena to more familiar ones from everyday life. Scientific papers, as well as textbooks and popular science articles, are packed with metaphors, analogies and intentional expressions. Like ERs, the use of metaphors and analogies is inevitable and necessary when communicating knowledge concerning molecular phenomena. Therefore, a large body of published research related to metaphors concerns science teachers’ and textbook writers’ interpretation and use of metaphors (Harrison & Treagust, 2006). In this paper we present a theoretical framework for examining metaphorical language use in relation to abstract phenomena and external representations. The framework was verified by using it to analyse students’ meaning-making in relation to an animation representing the sub-microscopic and abstract process of ATP-synthesis in Oxidative Phosphorylation. We seek to discover the animator’s intentions while designing the animation and to identify the metaphors that students use while interacting with the animation. Two of these metaphors serve as examples of a metaphor analysis, in which the characteristics of metaphors are outlined. To our knowledge,  no strategies to identify and understand the characteristics, benefits, and potential pitfalls of particular metaphors have, to date, been presented in science education research. Our aspiration is to contribute valuable insights into metaphorical language use at the interface between external representations, molecular processes, and student learning.