This article describes the motivation, design, analysis, and configuration of the criticality-aware multi-hop wireless communication protocol AirTight. Wireless communication has become a crucial part of the infrastructure of many cyber-physical applications. Many of these applications are real-time and also mixed-criticality, in that they have components/subsystems with different consequences of failure. Wireless communication is inevitably subject to levels of external interference. In this article, we represent this interference using a criticality-aware fault model; for each level of temporal interference in the fault model, we guarantee the timing behaviour of the protocol (i.e., we guarantee that packet deadlines are satisfied for certain levels of criticality). Although a new protocol, AirTight is built upon existing standards such as IEEE 802.15.4. A prototype implementation and protocol-accurate simulator have been produced. This article develops a series of schedulability analysis techniques for single-channel and multichannel wireless Cyber-Physical Systems (CPS). Heuristics are specified and evaluated as the starting point of design space exploration. Genetic algorithms are then defined and evaluated to assess their performance in developing schedule tables incorporating multichannel allocations in these systems.