Mechanical control of tissue growth: function follows form.

E arly biologists sought to identify vital life forces they believed responsible for the exquisite intricacy of tissue pattern and functional control. Later forms of ‘‘vitalism’’ downplayed the role of mystical powers and focused more on the importance of internal forces that emerged from the specific arrangement of tissue components, with particular emphasis on the role of reciprocal mechanical interactions among the material elements that constitute living systems. Many of these ideas were discarded when reductionist approaches became dominant, and, for the past 30 years, we have ‘‘explained’’ organogenesis and pattern formation almost exclusively in terms of the genes that control developmental signaling pathways. But we still do not understand how nature builds tissues with specialized form and function. Perhaps in part for this reason, there has been a recent resurgence of interest in mechanical forces as morphogenetic regulators. The work of Nelson et al. (1) in this issue of PNAS advances our understanding of the role of physics and architecture in developmental biology by focusing on a mechanical form of morphogenetic control that was proposed in the past (2, 3) but never before tested directly. Specifically, they experimentally address the question of whether the architectural form of a tissue can feed back to control cell growth patterns as a result of local variations of internal mechanical stresses that are distributed through the cytoskeleton and resisted by cell–cell and cell–extracellular matrix (ECM) adhesions.