In tissue engineering the main actors are the cells, as they define how tissue regeneration is going to occur. Therefore, a primary challenge in tissue engineering is controlling the cellular function in order to achieve reliable and repeatable tissue regeneration strategies. If tissue engineering provides commercial products, they should be reliable and safe for patients under all pathologies. For this challenge, it is also crucial to advance in the understanding of how cells sense and respond to their microenvironment, in particular to mechanical conditions in a process normally known as mechano-transduction. Hence, this chapter offers a brief description of how cells behave according to different microenvironmental conditions, specially focused on how cells interact with material and with other cells. In addition, a brief explanation is presented of how cells are able to sense and transduce these signals in a cellular response. Normally, cell nucleus is constantly exposed to biochemical signals and mechanical deformations, which together can modulate many cellular and nuclear functions. Finally, this chapter ends with the most relevant conclusions and, additionally, some questions are suggested to reinforce the different concepts and aspects covered in this chapter.