Anna Kendrick - George Clooney's sparring partner gets a 50/50 shot at stardom

It's not exactly a curse, but Anna Kendrick was such a glorious delight as Natalie Keener, George Clooney's fast-talking sparring partner in Up in the Air, that she has found it a mite difficult to shake the role off. While the industry goodwill generated by her Oscar-nominated performance gets her foot in the door, the gifted, appealing actress is now deluged with offers for what she calls, "uptight, ambitious, unfeeling girls". She keeps turning them down because, as the smart actors know, resting on your laurels is like having a 50-a-day smoking habit – it will shorten your life by several years.

Even when she does say "yes", as she did with the role of an inexperienced, try-too-hard therapist treating a 27-year-old cancer patient in 50/50, Kendrick deploys subterfuge to steer clear of Natalie. The makers of the comedy, including Seth Rogen as producer, would have been perfectly satisfied if she'd churned out some variation on Up in the Air's brisk corporate pixie in their film, but she had other ideas.

"I feel like I sort of tricked them into letting me play this part," smiles Kendrick, wearing a bathrobe over her street clothes in the hotel suite we meet in for no reason other than she wants to feel like "an old-time movie star".

"Katherine was almost foolishly confident on the page, but what I found interesting was the idea that she's got this office and she's got these patients but really she's pretending that she knows what she's doing."

Kendrick is 50/50's secret weapon, and she brings endearing vulnerability and comic precision to her portrayal of a professional woman slightly terrified she's going to be found out. First, the actress had to clear up a few misperceptions with Jonathan Levine, the Wackness director hired at the 11th hour after Nicole Holofcener departed the film for personal reasons.

"Someone had told me that she was based on a real girl whose father was a therapist so she felt like she had to be one, but I told Jonathan that didn't really make sense to me," says Kendrick. "And Will's therapist was a 65-year-old woman so it wasn't true" – Will is screenwriter/producer Will Reiser, and 50/50 is his funny, insightful, honest account of his experiences after being diagnosed with a malignant spinal tumour at the age of 26.

It focuses on the varied reactions of those around him – the friends who couldn't hack it and the ones who stood by his side, in particular best friend Rogen, who portrays himself in the film. For multiplex purposes, 50/50 has also been dressed up with a fictionalised romantic subplot, as Reiser's on-screen alter ego Adam – played by Joseph Gordon-Levitt – and Kendrick begin to fall for each other.

Their enchanting, nuanced scenes together are the beating heart of 50/50 – a marvel considering the actors were tossed in at the deep end. The Inception star was another late addition to 50/50, arriving on set in Vancouver a week into production after James McAvoy left for the birth of his son. The pair had 20 minutes of rehearsal, in a storage cupboard no less, before shooting their first scene.

"It's just a testament to Joe that he was able to create a connection in no time at all," marvels Kendrick, insisting that her first romantic role left her flat-footed and she relied on JGL ("I only call him that to my friends, to prove how cool I am") to guide her through. "I thought: 'This should be easy, we're just being adorable, right?' But sometimes it's easier to scream and spit, whereas doing something small and intimate is difficult."

The Maine-born actress, who earned her stripes in Broadway musicals (she was nominated for a Tony Award at 12) before landing her film debut in 2003's musical comedy Camp, isn't giving herself enough credit for her own contributions. One perception she is keen to shoot down, though, is the notion that her role as Bella Swan's best friend in the Twilight saga launched her career.

"I booked Up in the Air before the first Twilight even came out so it wasn't like I was going: 'Oh my god, this huge teen movie is out, I've got to make an adult movie as fast as I can!'" Equally, Edgar Wright hadn't seen the teen vampire series when he cast her as Michael Cera's bossy sister in Scott Pilgrim vs. the World. He had been won over by her turn as an over-achieving high-school debater in 2007's Rocket Science. Kendrick and Wright have been an item ever since.

That said the actress acknowledges that being part of the teen franchise has won her a fervent fanbase. "Twilight was this huge thing that spiralled out of control," observes Kendrick, who appears in part one of the series finale. Breaking Dawn. "When something gets that big, there's always a backlash. But I don't have people following me around everywhere, or writing horrendous things about me on the internet. I appreciate the fact that I get to reap all the benefits of this crazy mega-franchise with almost none of the bullshit that a lot of the cast has to deal with." The 26-year-old gets annoyed, however, when she hears people damning her career with faint praise.

"Somebody asked me recently why I play young professionals," says Kendrick, her voice rising in disbelief. "I thought: 'What am I supposed to be playing... a senior citizen?' But I don't define characters by their profession or age. It's just about what I feel that I can do with them." She's determined to find "just anything different", although ask if she'd like to sink her teeth into a juicy villain and Kendrick squeals.

"Oh my god," she says, suddenly breathless. "I'm one of those people who hadn't seen Mad Men until a couple months ago and I genuinely don't know how Vincent Kartheiser can play that character [slimy adman Pete Campbell] with no redeeming qualities. I actually had to ask myself: 'Could I be someone so horrible without trying to sneak in little moments where I apologise to the audience?' I really don't think I could."

So, villains are on hold for now. But the actress is staying busy. This year, she's done back-to-back shoots for a teen comedy, Rapturepalooza; an ensemble "dramedy" about five pregnant women, What to Expect When You're Expecting; and writer-director David Ayer's LAPD thriller End of Watch, in which she plays Jake Gyllenhaal's new wife, a dramatic change of pace for her. Meanwhile, it's back to rejecting the offers that keep coming in for uptight, ambitious, young professionals.

"50/50 was one of those rare occasions where it worked in my favour," she says. "But I do need to be careful."

'50/50' is out on 25 November; 'Twilight: Breaking Dawn – Part' 1 is out today