Between 1984 and 1986 I cycled 10,000 miles with only three pairs of 100% cotton jeans, a few T-shirts and a coat for cold weather. I cycled in driving rain, hot, cold, and blizzards where I couldn't see 10ft in front of me. I rarely felt uncomfortable (only when I got thoroughly soaked and a change of clothes fixed that) - never had any cause to replace the jeans with spandex trousers. I think the idea that jeans are uncomfortable for cycling is a myth pushed by spandex manufacturers. Sure, if the jeans are too tight, they'll be uncomfortable, but other than that, jeans are fine for cycling.

In my experience, synthetic clothing makes me sweat. Then it feels nasty and clingy and it stinks. Cotton breathes a lot better than any plastic material I've ever worn.

I think comfort is mainly in the mind - if you're convinced a material is going to be uncomfortable, it will be.