Substrate flexibility regulates growth and apoptosis of normal but not transformed cells
Department of Physiology
3T3 Cells; Animals; Apoptosis; Cell Division; Cell Line, Transformed; DNA; Mice; Reference Values; Substrate Specificity
Life Sciences | Medicine and Health Sciences
One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.
DOI of Published Version
Am J Physiol Cell Physiol. 2000 Nov;279(5):C1345-50.
American journal of physiology. Cell physiology
Wang H, Dembo M, Wang Y. (2000). Substrate flexibility regulates growth and apoptosis of normal but not transformed cells. Open Access Publications by UMMS Authors. https://doi.org/10.1152/ajpcell.2000.279.5.C1345. Retrieved from https://escholarship.umassmed.edu/oapubs/117