Gone are the long blonde locks of the invincible cheerleader who graced our screens in Heroes for four years. Instead, the actress has a cropped look that makes her seem older than her 21 years, set off by a cream satin shirt and black leather trousers.
"It changed my life," she says of the hit sci-fi show which began in 2006 and made her a household name around the globe before it was axed in May.
"I grew up on it and I was really lucky to be involved, but it turned my life upside down."
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Despite all the award nominations and success of the show, Panettiere has managed to stay grounded - something she credits to the cast and crew: "I dealt with the turmoil of new things happening in my life amongst a really great group of smart and down-to-earth people," she says.
"I had a lot of role models - people who put me back in my place if I started to wander - and a great family who keep me in line. I was surrounded by people who kept things in perspective for me."
Panettiere has been on TV in the US for most of her life - starting with a small role in 1996 in a show called Aliens In The Family.
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Now, all eyes are on how she copes with life after her breakthrough role in Heroes. She's already signed up to play Meredith Kercher's killer Amanda Knox in a controversial TV film - and she'll be heard on the big screen this month voicing a young female wolf in the animation Alpha And Omega.
It's a tale of two wolves - Kate and Humphrey (Justin Long) - who are childhood friends, but have no future together as Kate, the daughter of the pack leader, must marry a fellow Alpha wolf, while Humphrey's just an Omega, there to make the pack laugh.
But when they both get captured and taken to another park to 're-populate' it, they start falling for each other on the long journey home.
The actress is no stranger to animation, having played Dot in Pixar's A Bug's Life back in 1998, but she still finds it a strange experience: "I've definitely done uncomfortable things with voices, like you're going, 'Hi-yah' or howling, but it's a very different kind of art.
"You only have your voice to represent you, so you play around with it and do things you wouldn't normally do if you were standing on camera."
Panettiere admits, like her character Kate, she has "a pretty strong personality".
"I love her sense of selflessness - she knows what she needs to do for her family, to make sure there's enough food for everyone. She has to take on responsibility that wouldn't be her choice and put aside her own happiness so the rest of the pack can be happy and live. She's a really cool character to play."
While in Heroes, Panettiere dated her co-star Milo Ventimiglia, who played Peter Petrelli and is 12 years her senior. She's now in a relationship with Ukrainian boxer Wladimir Klitschko and the pair have been pictured on holiday in Croatia and enjoying the Munich beer festival.
At 6ft 6in, he's a good 15 inches taller than her and gossip columns have dubbed them the 'odd couple'.
She's adamant, however, that like the wolves in Alpha And Omega, we should be free to choose who we fall for.
"I don't think there's any kind of stereotype where you need to be with somebody who does the same job as you, or who's from the same walk of life or looks like you, is the same height as you...," she trails off, grinning.
"Sometimes you can't help who you fall in love with. And you should be allowed to be with whoever makes you happy."
The same philosophy could perhaps be applied to choosing acting roles in Panettiere's case, for her next performance will be as the brunette murderess Amanda Knox.
She's determined, following Heroes, she won't be typecast: "I definitely look like a certain type. Having blonde hair and playing a cheerleader a couple of times, it's difficult not to get slotted and be seen as something else.
"It either takes a period of time where the image of this character dies out in people's heads, or somebody takes a chance on you playing another role, letting you show people you're not just one thing.
"I was incredibly flattered and excited when I got the call and they asked me to play her."
Panettiere's aware of the tension surrounding the film - apparently Amanda Knox is not happy about it being made and is unlikely to let the actress meet her in prison.
"I've never played somebody who's a real person, still living and in a very controversial situation, but I'm looking forward to it. It's a really great script. I don't think anyone's going to be offended or upset with the way this film is put together."
And with that the actress, who clearly has her blonde head screwed on tight, sets off to cuddle a fluffy wolf on the red carpet for her new film.