When was the tipping point at which the united states could no longer be considered an isolated nation?

the protestant reformation's started in 1517, disturbing the religious and political order in europe´s catholic countries. the outcome was the european wars of religion prosecuted in europe in the 16th, 17th and part of the 18th century. nonetheless, uprisings, territorial disputes, and great power conflicts were also causes of the wars.  

answer; william penn's approach made the colony diverse by attracting many types of people and religions;