In professional interactive practices, space, time, human bodies, and material objects as well as written and oral language are dynamically implicated in a multimodal co-construction of meaning. A healthcare space – an operating room – is a typical example of such a social-semiotic, multimodal arrangement of communication modes which impacts the practices that are played out therein. Therefore, in designing healthcare spaces, it is important to allow for proactive inclusion and engagement of the categories of professionals who carry out their daily work in these spaces. Today, such involvement can be facilitated through mediation tools and simulation in Collaborative Virtual Environments (CVE). However, how collaboration unfolds and manifests at the micro-level of collaborative design interaction remains under-researched. The aim of this discussion paper is to introduce a social-semiotic approach to the analysis of multimodal collaborative design. We show how combinations of modes can trigger transformational shifts in levels of interaction.