As a way in, I'll start where lots of others do – with Thomas Pynchon.
What's the place of science (specifically, American science) in literature (specifically, American literature)? While literary scholars have written more about this than have historians, I think more dialogue's in order between historians of science and New Historicists.
He's a special case for reasons of both content and style. First: it's a commonplace to note the omnipresence of references to (and meditations on) science, technology, and their aftermath in his work. Second: Pynchon's well-known obsession with dialectics (order vs. entropy, free will vs. determinism, technology vs. nature, &c.) bleeds into his prose in the form of endless appositions, yoyo-ing run-ons, and the interplay of colloquial dialogue and technical digressions.
Both points matter for understanding the place of science in Pynchon's novels because they help us see that it's more than just one side of a binary (science vs. art, science vs. nature) – a misprision that often results from equating science with technology (bombs!) in the discussion of either's place in literary works. For Pynchon, science is more capacious. As Louis Menand put it in a review of Against the Day: "Science is either a method of disenchantment and control or it is a window onto possible worlds: it all depends on the application."
Pynchon's science opens up an older, wild potential – for both good and evil – that somehow feels more muted today. Menand, further on, calls Against the Day “a kind of inventory of the possibilities inherent in a particular moment in the history of the imagination," and concludes by suggesting that we read it like "a work of science fiction written in 1900." Literature's of its own time, to be sure, but historians might profit from the way it reframes the time in which it's set: 1890s Chicago, or, in the case of Mason & Dixon, the eighteenth-century mid-Atlantic.
In that novel (I won't even touch on the well-known cases in V, Gravity's Rainbow, or The Crying of Lot 49), we get a different science for a different age, though the same sense that it's wider than can be captured in the binary of The Two Cultures. Pynchon's project is the same as his surveyors': a path through chaos requires both saw and sextant, art and science, body and brain. As in Against the Day, science here is more than a referent. When L.E. Sissman called him "a mathematician of prose," he did justice to Pynchon's science as both a method and its results.
Understanding the place of science in literature means tracing its historical dimensions – what it meant for both author and characters. But it also means attending to literary matters – to style and composition – and it's this, I think, that's scared off many historians. Literary scholars note historians' flat-footedness on this turf – "Wider culture? Let's look at a novel!" – and they're right that, even though cultural history (of science) has a lot in common with literary scholarship (in the form of New Historicism), there's a lot of work left to be done at their boundary.