This is what I think the, "protect Nicole," thing was all about. She was definitely a hallucination, brought on not by the Marker, by Issac's hysterical desire to see her again. (This theory about Issac hallucinating is backed up by the bit in Chapter 2, when the locker door creaks open.) The door was never locked in the first place, it was only his mind that was keeping him there. Also, what's to say that he didn't hallucinate the necromorphs that attacked her. Another thing that supports this is that at the end, when Issac is trying to get into the shuttle, it is locked, but opens after a few seconds. This could be his realisation that it was not his fault that she died, and that he must survive.
This links in to my second theory, which is that Issac was crazy that whole time. I think that he had watched the whole Nicole video before even approaching the USG Ishimura. He edited it, and made himself forget about it, as the realisation that Nicole was dead would just break him. (Similar to Silent Hill 2.) That hallucination would give Issac the relief of saving Nicole, as he could not accept that she was dead. The crew members from the Kellion, Kendra and Hammond, are real for very little of the game. I think that the whole crew dies on that ship very early on, as you are first separated from them. They continue to appear in hallucinations as symbols for Issac's madness, (Hammond represents Issac's strong will and determination to carry on, Kendra represents Issac's regret and anger at himself for not being able to save Nicole. Even doctor Klein (I think) is representative of Issac's innocence and good-nature, and his SPOILERS***************************************************SPOILERS
death near the end is symbolic of Issac's need to punish himself for not saving Nicole.