Typical complex systems that involve microsensors and microactuators exhibit heterogeneity both at the implementation level and the problem level. For example, a system can be modeled using discrete events for digital circuits and SPICE-like analog descriptions for sensors. This heterogeneity exist not only in different implementation domains, but also at different level of abstraction. This naturally leads to a heterogeneous approach to system design that uses domain-specific models of computation (MoC) at various levels of abstractions to define a system, and leverages multiple CAD tools to do simulation, verification and synthesis. As the size and scope of the system increase, the integration becomes too difficult and unmanageable if different tools are coordinated using simple scripts. In addition, for MEMS devices and mixed-signal circuits, it is essential to integrate tools with different MoC to simulate the whole system. Ptolemy II, a heterogeneous system-level design tool, supports the interaction among different MoCs. This paper discusses heterogeneous CAD tool interoperability in the Ptolemy II framework. The key is to understand the semantic interface and classify the tools by their MoC and their level of abstraction. Interfaces are designed for each domain so that the external tools can be easily wrapped. Then the interoperability of the tools becomes the interoperability of the semantics. Ptolemy II can act as the standard interface among different tools to achieve the overall design modeling. A micro-accelerometer with digital feedback is studied as an example.