I never got over the 25 employees mark and probably that is one of the reasons why this problem never occurred but I can see your point and I think that once you reach a certain threshold (50 employees or so?) that it could be very hard to maintain such a culture. I'd also argue at the same time that once you do reach that level the moniker 'start-up' no longer applies to you. By that time you should have a solid business, the biggest risks should be behind you and you're transforming into a 'normal' company.

This line of thinking leads to yet another way to delineate what a start-up is: a start-up is a company where everybody knows everybody else.