Nowadays, several manufacturing systems are evolving towards a greater collaboration between human and robots. The development of such systems requires integrated design tasks involving many disciplines and domains such as systems engineering, safety analyses and multi-physics. Furthermore, the increasing presence of multiple and structured requirements makes the use of models inevitable during the designing phases and also strongly helpful during other phases of the system life-cycle. Besides, for a better efficiency, there is an increasing demand to have a Digital Twin of the system to be used for different purposes such as design improvements by playing different scenarios, virtual commissioning and controlling maintenance activities. In this paper, we first summarize the research context, the reference methodologies, and the emerging needs for Digital Twin creation. Then, we apply a design approach including Model-Based Systems Engineering (MBSE), Model-Based Safety Assessment (MBSA) and multi-physics modeling for the design of a collaborative workplace for the assembly of Electro-Mechanical Actuators on an aircraft wing. An operational flow to integrate MBSE, MBSA and multi-physics modelling activities is provided. Then, after having identified some relevant scientific barriers, we provide a meta-model for system models integration within a digital twin framework.