Science classroom discourse is inherently multimodal in that scientific meanings are made through an integration of multiple semiotic systems (e.g., language, diagrams, equations). Although some studies have described this multimodal nature, few have examined and explained the relationship between the integration of multiple semiotic systems and the instantiation of science content knowledge. Based on the notion of instantiation from systemic functional theory, this paper proposes a theoretical framework to account for how specific scientific meanings are instantiated in local acts of multimodal meaning-making. Using data from a series of nanoscience lessons, four exemplars of middle school students’ acts of meaning-making were analyzed to illustrate the theoretical framework. Specifically, each exemplar illustrates how a distinctive ideational meaning was instantiated through the co-deployment of verbal, visual, and gestural modes used in the students’ explanations of a physical phenomenon. This will be useful in furthering our understanding of the structure of science classroom discourse and its instantiation patterns in human semiosis.