Research led by MBI’s Yasuhiro Sawada, Associate Professor at the Department of Biological Sciences and the Division of Bioengineering, focuses on understanding how cells sense force and transduce mechanical signals. The process of mechanotranduction is important during development and disease, in such diverse contexts as neurogenesis, cardiac hypertrophy and carcinogenesis.
Our understanding of how external mechanical forces are transduced to intracellular signaling cascades leaves much to be resolved. A comprehensive picture of the molecular components and interactions that have a role in mechanotransduction is still evolving. Studies undertaken by Yasuhiro Sawada in the lab of Mike Sheetz have shed light on this biomechanical cascade by identifying p130CAS as a cytoskeletal mechanosensor employed during cell stretching . The identification of mechanoregulatory pathways continues to form the focus of work carried out by Sawada and colleagues.
Current research in the Sawada lab examines the role of mechanotransduction in stem cell differentiation. Mouse embryonic stem cells (mESCs) were used to test the effect of mechanical properties on the stem cell properties of pluripotency and differentiation. mESCs were grown on artificial substrates made of polyacrylamide gel, which were produced at different elasticities.
Sawada and colleagues looked at the effect of substrate elasticity on downstream biochemical signaling, focusing on the Src-ShcA-MAP kinase pathway. Using different chemicals to inhibit parts of this pathway, they were able to show how these signaling components effect the mechanical regulation of stem cell properties . These findings provide insight into methods for producing and maintaining mESCs in culture, which holds significance for the field of stem cell biology, therapy and regenerative medicine.
1. Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S, Sheetz MP. Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell. 2006 Dec 1;127(5):1015-26. [PMID: 17129785]
2. Shimizu T, Ueda J, Ho J C, Iwasaki K, Poellinger L, Harada I, Sawada Y. Dual Inhibition of Src and GSK3 Maintains Mouse Embryonic Stem Cells, Whose Differentiation Is Mechanically Regulated by Src Signaling. Stem Cells. 2012. In press.