Collaboration between startups and large firms is becoming increasingly necessary in the current context of open innovation, accelerating market demand and thus the increasingly rapid race to innovate. These asymmetrical partners, however, present significant differences that can generate a distance between them that can jeopardize the collaboration project. Beyond the dyad, other actors of the ecosystem, in particular innovation intermediaries, also participate in the collaborative project. The objective of this thesis is to bring out the factors fostering symbiotic collaboration between startups and large firms, based on an organizational and financial independence of the actors. This thesis also aims to show the interest of using the analogy with the biological symbiosis between symbionts interacting in a given ecosystem. The aim is thus to highlight the balance factors of the relationship, in a win-win perspective. Starting from the differences brought to light through cognitive distance, this research proposes to study the phenomenon of startup - large firm collaboration according to an exploratory approach and a mixed qualitative and quantitative method, based on the case method. The study of 38 cases carried out (leading to a data collection from 53 respondents in the form of interviews and survey) proposes a time-based, multi-perspective and holistic approach, mobilizing the theoretical framework of proximity (geographical, cognitive, social, organizational) and that of dynamic capabilities. This research resulted in four articles leading to several theoretical and managerial contributions. Firstly, the study from the startup's perspective allowed to identify the factors fostering proximity and collaboration between startups and large firms according to four levels: intra-organizational of the large firm, intra-organizational of the startup, inter-organizational and ecosystemic. Further exploration has then highlighted the complementary skills of startup founding teams, compared to solo startuppers, which is a source of proximity to large firms. The continuation of the study, from the perspective of large firms, brought to light the importance of a management based on collective intelligence as well as the evolving role of middle managers in large firms in the implementation of an open innovation strategy integrating a variety of actors, such as startups. Finally, the study of the perspective of innovation intermediaries regarding their roles in the development of startup - large firm collaboration has allowed these different roles to emerge according to three phases of the collaboration construction, including that of constituting an external resource for the large firm for the regeneration of its dynamic capabilities. A transversal contribution is also the identification and operationalization of the 2+1 phases of the collaboration along a chronological axis: the Upstream, Design and Process phases of the collaboration.