The Engler lab seeks to improve understanding of how the extracellular matrix (ECM), the 3-dimensional (3D) fibrillar scaffold to which cells adhere, directs the behavior of stem cells. Until recently, the ECM field focused on biochemical signals; Engler and his team have been influential in establishing the importance of mechanical signals in determining stem cell fate and organizing tissues. This specialization is enhanced by the lab’s interdisciplinarity, which allows them to apply engineering approaches to independently control the physical and biochemical properties of cellular scaffolds and modulate them in space and time to mimic in vivo variations.
The group’s research focus grew from Engler’s seminal Cell paper revealing that mechanical properties of the ECM are enough to determine stem cell fate: soft scaffolds yield neurons, stiff surroundings support bone differentiation, and intermediate properties support myogenesis. More recent breakthroughs include their demonstration that mesenchymal stem cells (MSCs) migrate in response to stiffness gradients (of a similar scale to those found in vivo) prior to differentiating, the first direct observation of migration in response to a physical gradient alone. Another key advance was their examination of the effect of temporal changes in ECM stiffness on myocardial precursors; by developing a material that stiffens at a similar rate to heart muscle during development, they observed that increasing stiffness enhances myocardial differentiation.
The Engler group is also actively translating their work into stem cell-based therapies for muscular dystrophy and to prevent heart failure following heart attacks. Towards the former, they have shown that adipose (fat) stem cells (ASCs) are capable of generating functional muscle units. Current efforts focus on efficient in vitro generation of myocytes from ASCs, as the stiffness of diseased muscle limits differentiation of directly injected naïve ASCs.
- Department of Bioengineering
- Materials Science and Engineering Program
- Biomedical Sciences Program
- Sanford Consortium for Regenerative Medicine
Meyer GA, Farris AL, Sato E, Gibbons M, Lane JG, Ward SR, Engler AJ. Muscle progenitor cell regenerative capacity in the torn rotator cuff. J Orthop Res 2015; 33(3):421-9.
Wen JH, Vincent LG, Fuhrmann A, Choi YS, Hribar KC, Taylor-Weiner H, Chen S, Engler AJ. Interplay of matrix stiffness and protein tethering in stem cell differentiation. Nat Mater 2014; 13: 979-987.
Young JL and Engler AJ. Hydrogels with time-dependent mechanical properties enhance cardiomyocyte differentiation in vitro. Biomaterials 2011; 32(4): 1002-1009